Prosthetic valve with tissue anchors free from lateral interconnections

ABSTRACT

Prosthetic valves and methods of use of prosthetic valves may be provided. In one implementation, a prosthetic valve for implantation within a native heart valve may be provided. The prosthetic valve may include an annular valve body having atrial anchoring arms and ventricular anchoring legs extending therefrom. The atrial anchoring arms and the ventricular anchoring legs may be configured for independent outward radial deflection. In some embodiments, at least one atrial anchoring arm may include first and third arm segments configured to extend in upstream directions and a second arm segment configured to extend in a downstream direction, the second arm segment situated between the first and third arm segments. The terminal end of the at least one atrial anchoring arm may be configured to be situated upstream from the rest of the arm when the prosthetic valve is radially-expanded.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/682,789, filed Aug. 22, 2017, now pending, which is a continuation ofU.S. patent application Ser. No. 15/541,783, filed Jul. 6, 2017, whichissued as U.S. Pat. No. 9,974,651 on May 22, 2018, which is a U.S.national stage entry under 35 U.S.C. § 371 of International ApplicationNo. PCT/IL2016/050125, filed Feb. 3, 2016, which claims priority fromU.S. Provisional Patent Application No. 62/112,343, filed Feb. 5, 2015,all of which are hereby incorporated by reference in their entirety.This application also claims priority from U.S. Provisional PatentApplication No. 62/560,384, filed Sep. 19, 2017, which is herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

Some embodiments of the present invention relate in general to valvereplacement. More specifically, some embodiments of the presentinvention relate to prosthetic valves for replacement of a cardiacvalve.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by thecombination of ischemic dysfunction of the papillary muscles, and thedilatation of the ventricle that is present in ischemic heart disease,with the subsequent displacement of the papillary muscles and thedilatation of the valve annulus.

Dilatation of the annulus of the valve prevents the valve leaflets fromfully coapting when the valve is closed. Regurgitation of blood from theventricle into the atrium results in increased total stroke volume anddecreased cardiac output, and ultimate weakening of the ventriclesecondary to a volume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some embodiments of the present invention, an implant is providedhaving a tubular portion, an upstream support portion and one or moreflanges. The implant is percutaneously deliverable to a native heartvalve in a compressed state, and is expandable at the native valve. Theimplant and its delivery system facilitate causing the upstream supportportion and the flanges to protrude radially outward from the tubularportion without expanding the tubular portion. Expansion of the tubularportion brings the upstream support portion and the flanges closertogether, for securing the implant at the native valve by sandwichingtissue of the native valve between the upstream support portion and theflanges.

In accordance with an embodiment of the present invention, an apparatusis provided for use with a native valve that is disposed between anatrium and a ventricle of a heart of a subject, the apparatus including:a valve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis, the tubular portion defining a plurality of valve-frame couplingelements disposed circumferentially around the longitudinal axis; aplurality of prosthetic leaflets, coupled to the frame, disposed withinthe lumen, and arranged to provide unidirectional flow of blood from anupstream end of the lumen to a downstream end of the lumen; an outerframe: including a ring defined by a pattern of alternating peaks andtroughs, the peaks being longitudinally closer to the upstream end thanto the downstream end, and the troughs being longitudinally closer tothe downstream end than to the upstream end, and the pattern of the ringhaving an amplitude longitudinally between the peaks and the troughs,including a plurality of legs, each of the legs coupled to the ring at arespective trough, and shaped to define a plurality of outer-framecoupling elements, each of the outer-frame coupling elements (i) coupledto the ring at a respective peak, and (ii) fixed with respect to arespective valve-frame coupling element, and: the tubular portion has(i) a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the outer-frame coupling elements to the valve-framecoupling elements is such that compression of the tubular portion fromthe expanded state toward the compressed state such that the valve-framecoupling elements pull the outer-frame coupling elements radiallyinward: (i) reduces a circumferential distance between each of theouter-frame coupling elements and its adjacent outer-frame couplingelements, and (ii) increases the amplitude of the pattern of the ring.

In an embodiment, the ring circumscribes the tubular portion.

In an embodiment, the valve-frame coupling elements are disposedcircumferentially around the longitudinal axis between the upstream endand the downstream end but not at the upstream end nor at the downstreamend.

In an embodiment, the upstream support portion includes one or morefabric pockets disposed circumferentially, each pocket of the one ormore pockets having an opening that faces a downstream direction.

In an embodiment, the outer frame is coupled to the valve frame only viathe fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

In an embodiment, the apparatus further includes an upstream supportportion that includes a plurality of arms that extend radially from thetubular portion, and the upstream support portion has (i) aconstrained-arm state, and (ii) a released-arm state in which the armsextend radially outward from the tubular portion, each leg has atissue-engaging flange that has (i) a constrained-flange state, and (ii)a released-flange state in which the flange extends radially outwardfrom the tubular portion, and the apparatus has an intermediate state inwhich (i) the tubular portion is in its compressed state, (ii) theupstream support portion is in its released-arm state, and (iii) thelegs are in their released-flange state.

In an embodiment, the apparatus includes an implant that includes thevalve frame, the leaflets, and the outer frame, and the apparatusfurther includes a tool: including a delivery capsule dimensioned (i) tohouse and retain the implant in a compressed state of the implant inwhich (a) the tubular portion is in its compressed state, (b) theupstream support portion is in its constrained-arm state, and (c) thelegs are in their constrained-flange state, and (ii) to be advancedpercutaneously to the heart of the subject while the implant is housedand in its compressed state, and operable from outside the subject to:transition the implant from its compressed state into the intermediatestate while retaining the tubular portion in its compressed state, andsubsequently, expand the tubular portion toward its expanded state.

In an embodiment, the tool is operable from outside the subject totransition the implant from its compressed state into the intermediatestate by (i) releasing the legs into their released-flange state, whileretaining the tubular portion in its compressed state, and (ii)subsequently, releasing the upstream support portion into itsreleased-arm state, while retaining the tubular portion in itscompressed state.

In an embodiment, the tool is operable from outside the subject totransition the implant from its compressed state into the intermediatestate by (i) releasing the upstream support portion into itsreleased-arm state, while retaining the tubular portion in itscompressed state, and (ii) subsequently, releasing the legs into theirreleased-flange state, while retaining the tubular portion in itscompressed state.

In an embodiment, the fixation of the outer-frame coupling elements tothe valve-frame coupling elements is such that, when the apparatus is inits intermediate state, expansion of the tubular portion from itscompressed state toward its expanded state moves the flangeslongitudinally away from the valve-frame coupling elements.

In an embodiment, the fixation of the outer-frame coupling elements tothe valve-frame coupling elements is such that, when the apparatus is inits intermediate state, expansion of the tubular portion from acompressed state toward an expanded state reduces the amplitude of thepattern of the ring and passes the flanges between the arms.

In an embodiment, the upstream support portion further includes acovering that covers the arms to form an annular shape in thereleased-arm state, and, when the apparatus is in its intermediatestate, expansion of the tubular portion from its compressed state towardits expanded state presses the flanges onto the covering.

In an embodiment, in the compressed state of the tubular portion, adownstream end of each leg of the tubular portion is longitudinallycloser than the valve-frame coupling elements to the downstream end, andthe flange of each leg is disposed longitudinally closer than thevalve-frame coupling elements to the upstream end.

In an embodiment, in the expanded state of the tubular portion, thedownstream end of each leg is longitudinally closer than the valve-framecoupling elements to the downstream end, and the flange of each leg isdisposed longitudinally closer than the valve-frame coupling elements tothe upstream end.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus having an implant that includes: a valve frame that includes atubular portion that circumscribes a longitudinal axis of the valveframe so as to define a lumen along the axis, the tubular portion havingan upstream end, a downstream end, a longitudinal length therebetween,and a diameter transverse to the longitudinal axis; a valve member,coupled to the tubular portion, disposed within the lumen, and arrangedto provide unidirectional upstream-to-downstream flow of blood throughthe lumen; an upstream support portion, coupled to the tubular portion;and an outer frame, coupled to the tubular portion, and including atissue-engaging flange, and: the implant has a first state and a secondstate, in both the first state and the second state, (i) the upstreamsupport portion extends radially outward from the tubular portion, and(ii) the tissue-engaging flange extends radially outward from thetubular portion, and the tubular portion, the upstream support portion,and the outer frame are arranged such that transitioning of the implantfrom the first state toward the second state: increases the diameter ofthe tubular portion by a diameter-increase amount, decreases the lengthof the tubular portion by a length-decrease amount, and moves the flangea longitudinal distance toward or toward-and-beyond the upstream supportportion, the distance being greater than the length-decrease amount.

In an embodiment of the present invention, the tubular portion, theupstream support portion, and the outer frame may be arranged such thatthe longitudinal distance is more than 20 percent greater than thelength-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, andthe outer frame may be arranged such that the longitudinal distance ismore than 30 percent greater than the length-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, andthe outer frame may be arranged such that the longitudinal distance ismore than 40 percent greater than the length-decrease amount.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve that is disposed between an atrium and aventricle of a heart of a subject is provided, the apparatus including:a valve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis; a plurality of prosthetic leaflets, coupled to the frame, disposedwithin the lumen, and arranged to provide unidirectional flow of bloodfrom an upstream end of the lumen to a downstream end of the lumen; anouter frame, including: a ring defined by a pattern of alternating peaksand troughs: the peaks being longitudinally closer than the troughs tothe upstream end, the peaks being fixed to respective sites of thetubular portion at respective coupling points disposed circumferentiallyaround the longitudinal axis, and the pattern of the ring having anamplitude longitudinally between the peaks and the troughs; and aplurality of legs, each of the legs coupled to the ring at a respectivetrough, and: the tubular portion has (i) a compressed state in which thetubular portion has a compressed diameter, and (ii) an expanded state inwhich the tubular portion has an expanded diameter that is greater thanthe compressed diameter, and the fixation of the peaks to the respectivesites of the tubular portion is such that compression of the tubularportion from the expanded state toward the compressed state such thatthe respective sites of the tubular portion pull the peaks radiallyinward via radially-inward tension on the coupling points: (i) reduces acircumferential distance between each of the coupling points and itsadjacent coupling points, and (ii) increases the amplitude of thepattern of the ring.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve that is disposed between an atrium and aventricle of a heart of a subject is provided, the apparatus including:a valve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis, the valve frame defining a plurality of valve-frame couplingelements disposed circumferentially around the longitudinal axis; aplurality of prosthetic leaflets, coupled to the frame, disposed withinthe lumen, and arranged to provide unidirectional flow of blood from anupstream end of the lumen to a downstream end of the lumen; an outerframe: including a ring defined by a pattern of alternating peaks andtroughs, the peaks being longitudinally closer to the upstream end thanto the downstream end, and the troughs being longitudinally closer tothe downstream end than to the upstream end, and the pattern of the ringhaving an amplitude longitudinally between the peaks and the troughs,including a plurality of legs, each of the legs coupled to the ring at arespective trough, and shaped to define a plurality of outer-framecoupling elements, each of the outer-frame coupling elements (i) coupledto the ring at a respective peak, and (ii) fixed with respect to arespective valve-frame coupling element, and: the tubular portion has(i) a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the outer-frame coupling elements with respect to thevalve-frame coupling elements is such that compression of the tubularportion from the expanded state toward the compressed state (i) pullsthe outer-frame coupling elements radially inward via radially-inwardpulling of the valve-frame coupling elements on the outer-frame couplingelements, (ii) reduces a circumferential distance between each of theouter-frame coupling elements and its adjacent outer-frame couplingelements, and (iii) increases the amplitude of the pattern of the ring,without increasing a radial gap between the valve frame and the ring bymore than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

There is further provided, in accordance with an embodiment of thepresent invention, an apparatus for use with a native valve that isdisposed between an atrium and a ventricle of a heart of a subject isprovided, the apparatus including: a valve frame, including a tubularportion that circumscribes a longitudinal axis of the valve frame so asto define a lumen along the axis; a plurality of prosthetic leaflets,coupled to the frame, disposed within the lumen, and arranged to provideunidirectional flow of blood from an upstream end of the lumen to adownstream end of the lumen; an outer frame, including: a ring definedby a pattern of alternating peaks and troughs: the peaks beinglongitudinally closer than the troughs to the upstream end, the peaksbeing fixed to respective sites of the tubular portion at respectivecoupling points disposed circumferentially around the longitudinal axis,and the pattern of the ring having an amplitude longitudinally betweenthe peaks and the troughs; and a plurality of legs, each of the legscoupled to the ring at a respective trough, and: the tubular portion has(i) a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the peaks to the respective sites of the tubular portion issuch that compression of the tubular portion from the expanded statetoward the compressed state (i) pulls the peaks radially inward viaradially-inward pulling of the respective sites of the tubular portionon the peaks, (ii) reduces a circumferential distance between each ofthe coupling points and its adjacent coupling points, and (iii)increases the amplitude of the pattern of the ring, without increasing aradial gap between the valve frame and the ring by more than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including: a valveframe, including a tubular portion that circumscribes a longitudinalaxis of the valve frame so as to define a lumen along the axis, thetubular portion having an upstream end, a downstream end, and defining aplurality of valve-frame coupling elements disposed circumferentiallyaround the longitudinal axis between the upstream end and the downstreamend but not at the upstream end nor at the downstream end; a pluralityof prosthetic leaflets, disposed within the lumen, and arranged toprovide unidirectional flow of blood through the lumen; an outer frame:including a ring defined by a pattern of alternating peaks and troughs,the peaks being longitudinally closer to the upstream end than to thedownstream end, and the troughs being longitudinally closer to thedownstream end than to the upstream end, including a plurality of legs,each of the legs coupled to the ring at a respective trough, and shapedto define a plurality of outer-frame coupling elements, each of theouter-frame coupling elements (i) coupled to the ring at a respectivepeak, and (ii) fixed with respect to a respective valve-frame couplingelement at a respective coupling point, and: the tubular portion has (i)a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, andexpansion of the tubular portion from the compressed state toward theexpanded state (i) increases a circumferential distance between each ofthe outer-frame coupling elements and its adjacent outer-frame couplingelements, and (ii) moves the plurality of legs in a longitudinallyupstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including: a valveframe, including a tubular portion that circumscribes a longitudinalaxis of the valve frame so as to define a lumen along the axis, thetubular portion having an upstream end and a downstream end; a pluralityof prosthetic leaflets, disposed within the lumen, and arranged toprovide unidirectional flow of blood through the lumen; an outer frame,including: a ring defined by a pattern of alternating peaks and troughs:the peaks being longitudinally closer than the troughs to the upstreamend, the peaks being fixed to respective sites of the tubular portion atrespective coupling points disposed circumferentially around thelongitudinal axis between the upstream end and the downstream end butnot at the upstream end nor the downstream end; and a plurality of legs,each of the legs coupled to the ring at a respective trough, and: thetubular portion has (i) a compressed state in which the tubular portionhas a compressed diameter, and (ii) an expanded state in which thetubular portion has an expanded diameter that is greater than thecompressed diameter, and expansion of the tubular portion from thecompressed state toward the expanded state (i) increases acircumferential distance between each of the coupling points and itsadjacent coupling points, and (ii) moves the plurality of legs in alongitudinally upstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including: a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding: a valve frame, including: a tubular portion having anupstream end and a downstream end, and shaped to define a lumentherebetween, and an upstream support portion, extending from theupstream end of the tubular portion; and at least one leg, coupled tothe valve frame at a coupling point, and having a tissue-engagingflange; and a valve member disposed within the lumen, and configured tofacilitate one-way liquid flow through the lumen from the upstream endof the tubular portion to the downstream end of the tubular portion, andthe frame assembly: has a compressed state, for percutaneous delivery tothe heart, in which the tubular portion has a compressed diameter, isbiased to assume an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and isconfigured such that increasing the diameter of the tubular portiontoward the expanded diameter causes longitudinal movement: of theupstream support portion toward the coupling point, and of thetissue-engaging flange away from the coupling point.

In an embodiment: the apparatus includes an implant that includes theframe assembly and the valve member, and the apparatus further includesa tool: including a delivery capsule dimensioned (i) to house and retainthe implant in the compressed state, and (ii) to be advancedpercutaneously to the heart of the subject while the implant is housedand in the compressed state, and operable from outside the subject tofacilitate an increase of the diameter of the tubular portion from thecompressed diameter toward the expanded diameter such that the increaseof the diameter actuates longitudinal movement: of the upstream supportportion toward the coupling point, and of the tissue-engaging flangeaway from the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes longitudinal movement of theupstream end of the tubular portion toward the coupling point.

In an embodiment, the coupling point is disposed closer to thedownstream end of the frame assembly than are either the tissue-engagingflange or the upstream support portion.

In an embodiment, in the expanded state of the frame assembly, the legextends away from the central longitudinal axis.

In an embodiment, the expanded state of the frame assembly may be afully-expanded state of the frame assembly, the leg is expandable intoan expanded state of the leg, independently of increasing the diameterof the tubular portion, and in the expanded state of the leg, the legextends away from the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, the legextends away from the central longitudinal axis, and in the compressedstate of the frame assembly, the leg is generally parallel with thecentral longitudinal axis.

In an embodiment, the frame assembly may be configured such that thelongitudinal movement of the tissue-engaging flange away from thecoupling point is a translational movement of the tissue-engaging flangethat does not include rotation of the tissue-engaging flange.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes 1-20 mm of longitudinalmovement of the tissue-engaging flange away from the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes 1-20 mm of longitudinalmovement of the upstream support portion toward the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state reduces a distance between theupstream support portion and the tissue-engaging flange by 5-30 mm.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state moves the tissue-engaging flangelongitudinally past the upstream support portion.

In an embodiment, the tubular portion may be defined by a plurality ofcells of the valve frame, and increasing the diameter of the tubularportion by expanding the frame assembly toward the expanded state:includes (i) increasing a width, orthogonal to the longitudinal axis ofthe frame assembly, of each cell, and (ii) reducing a height, parallelwith the longitudinal axis of the frame assembly, of each cell, andcauses longitudinal movement of the upstream support portion toward thecoupling point by reducing a height, parallel with the longitudinal axisof the frame assembly, of the tubular portion, by reducing the height ofeach cell.

In an embodiment, the leg is disposed on an outside of the tubularportion.

In an embodiment, the at least one leg includes a plurality of legs, thecoupling point includes a plurality of coupling points, and the frameassembly includes a leg frame that circumscribes the tubular portion,includes the plurality of legs, and is coupled to the valve frame at theplurality of coupling points, such that the plurality of legs isdistributed circumferentially around the tubular portion.

In an embodiment, the plurality of coupling points is disposedcircumferentially around the frame assembly on a transverse plane thatis orthogonal to the longitudinal axis of the frame assembly.

In an embodiment, the plurality of legs may be coupled to the valveframe via a plurality of struts, each strut having a first end that iscoupled to a leg of the plurality of legs, and a second end that iscoupled to a coupling point of the plurality of coupling points, in thecompressed state of the frame assembly, being disposed at a first anglein which the first end is disposed closer to the downstream end of theframe assembly than is the second end, and being deflectable withrespect to the coupling point of the plurality of coupling points, suchthat increasing the diameter of the tubular portion by expanding theframe assembly toward the expanded state causes the strut to deflect toa second angle in which the first end is disposed further from thedownstream end of the frame assembly than is the first end in thecompressed state of the frame assembly.

In an embodiment, the leg frame may be structured such that each leg ofthe plurality of legs is coupled to two struts of the plurality ofstruts, and two struts of the plurality of struts are coupled to eachcoupling point of the plurality of coupling points.

In an embodiment, the leg may be coupled to the valve frame via a strut,the strut having a first end that is coupled to the leg, and a secondend that is coupled to the coupling point, in the compressed state ofthe frame assembly, being disposed at a first angle in which the firstend is disposed closer to the downstream end of the frame assembly thanis the second end, and being deflectable with respect to the couplingpoint, such that increasing the diameter of the tubular portion byexpanding the frame assembly toward the expanded state causes the strutto deflect to a second angle in which the first end is disposed furtherfrom the downstream end of the frame assembly than is the first end inthe compressed state of the frame assembly.

In an embodiment, the at least one leg includes at least a first leg anda second leg.

In an embodiment, the first leg and the second leg are both coupled tothe valve frame at the coupling point.

In an embodiment, the first leg may be coupled to the coupling point viaa respective first strut, and the second leg is coupled to the couplingpoint via a respective second strut.

In an embodiment, the first and second legs, the first and secondstruts, and the coupling point are arranged such that, in the expandedstate of the frame assembly: the coupling point is disposed,circumferentially with respect to the tubular portion, between the firststrut and the second strut, the first strut is disposed,circumferentially with respect to the tubular portion, between thecoupling point and the first leg, and the second strut is disposed,circumferentially with respect to the tubular portion, between thecoupling point and the second leg.

In an embodiment, the coupling point includes at least a first couplingpoint and a second coupling point.

In an embodiment, the leg is coupled to the valve frame at the firstcoupling point and at the second coupling point.

In an embodiment, the leg may be coupled to the first coupling point viaa respective first strut, and to the second coupling point via arespective second strut.

In an embodiment, the first and second legs, the first and secondstruts, and the coupling point are arranged such that, in the expandedstate of the frame assembly: the leg is disposed, circumferentially withrespect to the tubular portion, between the first strut and the secondstrut, the first strut is disposed, circumferentially with respect tothe tubular portion, between the leg and the first coupling point, andthe second strut is disposed, circumferentially with respect to thetubular portion, between the leg and the second coupling point.

In an embodiment, in the expanded state of the frame assembly, theupstream support portion extends radially outward from the tubularportion.

In an embodiment, the expanded state of the frame assembly is afully-expanded state of the frame assembly, the upstream support portionis expandable into an expanded state of the upstream support portion,independently of increasing the diameter of the tubular portion, and inthe expanded state of the upstream support portion, the upstream supportportion extends radially outward from the tubular portion.

In an embodiment, in the compressed state of the frame assembly, theupstream support portion is generally tubular, collinear with thetubular portion, and disposed around the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, an innerregion of the upstream support portion extends radially outward from thetubular portion at a first angle with respect to the tubular portion,and an outer region of the upstream support portion extends, from theinner region of the upstream support portion, further radially outwardfrom the tubular portion at a second angle with respect to the tubularportion, the second angle being smaller than the first angle.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding: a valve frame, including: a tubular portion having anupstream end and a downstream end, and shaped to define a lumentherebetween, and an upstream support portion, extending from theupstream end of the tubular portion; and at least one leg, coupled tothe valve frame at a coupling point, and having a tissue-engagingflange; and a valve member disposed within the lumen, and configured tofacilitate one-way liquid flow through the lumen from the upstream endof the tubular portion to the downstream end of the tubular portion, andthe frame assembly: has a compressed state, for percutaneous delivery tothe heart, in which the tubular portion has a compressed diameter, isbiased to assume an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and isconfigured such that reducing the diameter of the tubular portion towardthe compressed diameter causes longitudinal movement of the upstreamsupport portion away from the coupling point, and of the tissue-engagingflange toward the coupling point.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, including:a valve frame, including: a tubular portion having an upstream end and adownstream end, and shaped to define a lumen therebetween, and anupstream support portion, extending from the upstream end of the tubularportion; and at least one leg, coupled to the valve frame at a couplingpoint, and having a tissue-engaging flange; and a valve member disposedwithin the lumen, and configured to facilitate one-way liquid flowthrough the lumen from the upstream end of the tubular portion to thedownstream end of the tubular portion, and the frame assembly: has acompressed state, for percutaneous delivery to the heart, isintracorporeally expandable into an expanded state in which a diameterof the tubular portion is greater than in the compressed state, and isconfigured such that increasing the diameter of the tubular portion byexpanding the frame assembly toward the expanded state causeslongitudinal movement of the tissue-engaging flange away from thecoupling point.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding: an inner frame including an inner-frame tubular portion thatcircumscribes the central longitudinal axis, has an upstream end and adownstream end, and defines a channel therebetween, the inner framedefining a plurality of inner-frame couplings disposed circumferentiallyat a longitudinal location of the inner frame, an outer frame includingan outer-frame tubular portion that coaxially circumscribes at least aportion of the inner-frame tubular portion, the outer frame defining aplurality of outer-frame couplings disposed circumferentially at alongitudinal location of the outer frame, and a plurality of connectors,each connector connecting a respective inner-frame coupling to arespective outer-frame coupling; a liner, disposed over at least part ofthe inner-frame tubular portion; and a plurality of prosthetic leaflets,coupled to the inner-frame tubular portion and disposed within thechannel, and: the frame assembly: (i) is compressible by aradially-compressive force into a compressed state in which the innerframe is in a compressed state thereof and the outer frame is in acompressed state thereof, (ii) is configured, upon removal of theradially-compressive force, to automatically expand into an expandedstate thereof in which the inner frame is in an expanded state thereofand the outer frame is in an expanded state thereof, in the expandedstate of the frame assembly, the prosthetic leaflets are configured tofacilitate one-way fluid flow, in a downstream direction, through thechannel, and the connection of the inner-frame couplings to therespective outer-frame couplings is such that expansion of the frameassembly from the compressed state to the expanded state causes theinner-frame tubular portion to slide longitudinally in a downstreamdirection with respect to the outer-frame tubular portion.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including: a tubularportion, having an upstream portion that includes an upstream end, and adownstream portion that includes a downstream end, and shaped to definea lumen between the upstream portion and the downstream portion; aplurality of prosthetic leaflets, disposed within the lumen, andarranged to provide unidirectional flow of blood from the upstreamportion to the downstream portion; an annular upstream support portion:having an inner portion that extends radially outward from the upstreamportion, and including one or more fabric pockets disposedcircumferentially around the inner portion, each pocket of the one ormore pockets having an opening that faces a downstream direction.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, at the inner portion of the upstream supportportion, the covering is closely-fitted between the radially-inner partsof the arms, and at the outer portion of the upstream support portion,the pockets are formed by the covering being loosely-fitted between theradially-outer parts of the arms.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, the radially-outer part being more flexiblethan the radially-inner part.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, at the outer portion of the upstream supportportion, the pockets are formed by each arm curving to form a hookshape.

In an embodiment, each pocket may be shaped and arranged to billow inresponse to perivalvular flow of blood in an upstream direction.

In an embodiment, the apparatus may be configured to be transluminallydelivered to the heart and implanted at the native valve by expansion ofthe apparatus, such that the upstream support portion is disposed in theatrium and the tubular portion extends from the upstream support portioninto the ventricle, and each pocket is shaped and arranged such thatperivalvular flow of blood in an upstream direction presses the pocketagainst tissue of the atrium.

In accordance with an embodiment of the present invention, an apparatusis provided including a plurality of prosthetic valve leaflets; and aframe assembly, including: a tubular portion defined by a repeatingpattern of cells, the tubular portion extending circumferentially arounda longitudinal axis so as to define a longitudinal lumen, the prostheticvalve leaflets coupled to the inner frame and disposed within the lumen;an outer frame, including a plurality of legs, distributedcircumferentially around the tubular portion, each leg having atissue-engaging flange; an upstream support portion that includes aplurality of arms that extend radially outward from the tubular portion;and a plurality of appendages, each having a first end that defines acoupling element via which the tubular portion is coupled to the outerframe, and a second end; and the frame assembly defines a plurality ofhubs, distributed circumferentially around the longitudinal axis on aplane that is transverse to the longitudinal axis, each hub defined byconvergence and connection of, (i) two adjacent cells of the tubularportion, (ii) an arm of the plurality of arms, and (iii) an appendage ofthe plurality of appendages.

In an embodiment, each hub has six radiating spokes, two of the sixspokes being part of a first cell of the two adjacent cells, two of thesix spokes being part of a second cell of the two adjacent cells, one ofthe six spokes being the arm, and one of the six spokes being the secondend of the appendage.

In an embodiment, the appendages are in-plane with the tubular portion.

In an embodiment, the appendages are in-plane with the outer frame.

In accordance with an embodiment of the present invention, a method foruse with a native valve of a heart of a subject is provided, the methodincluding percutaneously advancing to heart, an implant: including avalve frame, a valve member disposed within a lumen defined by the valveframe, and at least one leg, coupled to the valve frame at a couplingpoint, and having an upstream end, a downstream end, and a centrallongitudinal axis therebetween; positioning the implant within the heartsuch that a tissue-engaging flange of the leg is disposed downstream ofthe valve, and thereafter causing the flange to protrude radiallyoutward from the axis; subsequently, while an upstream support portionof the valve frame is disposed upstream of the valve, causing theupstream support portion to protrude radially outward from the axis,such that tissue of the valve is disposed between the upstream supportportion and the flange; and subsequently, sandwiching the tissue betweenthe upstream support portion and the flange by reducing a distancebetween the upstream support portion and the flange by causinglongitudinal movement (i) of the upstream support portion toward thecoupling point, and (ii) of the tissue-engaging flange away from thecoupling point.

In an embodiment, causing the longitudinal movement (i) of the upstreamsupport portion toward the coupling point, and (ii) of thetissue-engaging flange away from the coupling point, includes causingthe longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present invention, a method foruse with a native valve of a heart of a subject is provided, the methodincluding percutaneously advancing to heart, an implant: including avalve frame, a valve member disposed within a lumen defined by the valveframe, and at least one leg, coupled to the valve frame at a couplingpoint, and having an upstream end, a downstream end, and a centrallongitudinal axis therebetween; positioning the implant within the heartsuch that an upstream support portion of the valve frame is disposedupstream of the valve, and thereafter causing the upstream supportportion to protrude radially outward from the axis; subsequently, whilea tissue-engaging flange of the leg is disposed downstream of the valve,causing the tissue-engaging flange to protrude radially outward from theaxis, such that tissue of the valve is disposed between the upstreamsupport portion and the flange; and subsequently, sandwiching the tissuebetween the upstream support portion and the flange by reducing adistance between the upstream support portion and the flange by causinglongitudinal movement (i) of the upstream support portion toward thecoupling point, and (ii) of the tissue-engaging flange away from thecoupling point.

In an embodiment, causing the longitudinal movement (i) of the upstreamsupport portion toward the coupling point, and (ii) of thetissue-engaging flange away from the coupling point, includes causingthe longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present invention, a method foruse with a native valve of a heart of a subject is provided, the methodincluding: percutaneously advancing an implant to the heart, the implanthaving an upstream end, a downstream end, and a central longitudinalaxis therebetween, and including a tubular portion, an upstream supportportion, and a plurality of tissue-engaging flanges; positioning theimplant within the heart such that the upstream support portion isdisposed upstream of the valve, positioning the implant within the heartsuch that the tissue-engaging flanges are disposed downstream of thevalve, without increasing a diameter of the tubular portion: causing theupstream support portion to extend radially outward from the axis so asto have a first support-portion span, and causing the flanges to extendradially outward from the axis so as to have a first flange span; andsubsequently, causing the upstream support portion and the flanges movetoward each other by at least 5 mm by increasing a diameter of thetubular portion such that: the upstream support portion extends radiallyoutward so as to have a second support-portion span, the firstsupport-portion span being at least 40 percent as great as the secondsupport-portion span, and the flanges extend radially outward so as tohave a second flange span, the first flange span being at least 30percent as great as the second flange span.

There is further provided, in accordance with an application of thepresent invention, a method for use with a native valve of a heart of asubject, the method including: percutaneously advancing an implant tothe heart, the implant: having an upstream end, a downstream end, and acentral longitudinal axis therebetween, and including a tubular portion,an upstream support portion, and a plurality of tissue-engaging flanges;positioning the implant within the heart such that the upstream supportportion is disposed upstream of the valve, positioning the implantwithin the heart such that the tissue-engaging flanges are disposeddownstream of the valve, without increasing a diameter of the tubularportion: causing the upstream support portion to extend radially outwardfrom the axis, and causing the flanges to extend radially outward fromthe axis so as to have a first flange span; and subsequently, byincreasing a diameter of the tubular portion: causing the upstreamsupport portion and the flanges move toward each other by at least 5 mm,causing the upstream support portion to move further radially outwardfrom the axis, and causing each flange of the plurality of flanges totranslate radially outward so as to have a second flange span that isgreater than the first flange span.

The present invention will be more fully understood from the followingdetailed description of applications thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B and 2A-E are schematic illustrations of an implant for usewith a native valve of a heart of a subject, in accordance with someapplications of the invention;

FIGS. 3A-C are schematic illustrations that show structural changes in aframe assembly during transitioning of the assembly between itscompressed and expanded states, in accordance with some applications ofthe invention;

FIGS. 4A-F are schematic illustrations of implantation of the implant atthe native valve, in accordance with some applications of the invention;

FIG. 5 is a schematic illustration of a step in the implantation of theimplant, in accordance with some applications of the invention;

FIG. 6 is a schematic illustration of the implant, in accordance withsome applications of the invention;

FIGS. 7A-B and 8A-B are schematic illustrations of frame assemblies ofrespective implants, in accordance with some applications of theinvention; and

FIGS. 9A-C are schematic illustrations of an implant including a frameassembly, in accordance with some applications of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-B and 2A-E, which are schematicillustrations of an implant 20 (alternatively, “prosthetic valve 20”)for use with a native valve of a heart of a subject, in accordance withsome embodiments of the invention. Prosthetic valve 20 includes a frameassembly 22 that has an upstream end 24 (alternatively, “atrial end24”), a downstream end 26 (alternatively, “ventricular end 26”), and acentral longitudinal axis ax1 therebetween. The term “atrial end” mayrefer to an end of a given feature which is configured to be situatedclosest to an atrium of the heart when prosthetic valve 20 is implantedtherein. For example, in FIGS. 1A, 1B, and 2A-2E, the atrial end ofprosthetic valve 20 may be the top end of prosthetic valve 20.Similarly, the term “ventricular end” may refer to an end of a givenfeature which is configured to be situated closest to a ventricle of theheart when prosthetic valve 20 is implanted therein. For example, inFIGS. 1A, 1B, and 2A-2E, the ventricular end of prosthetic valve 20 maybe the bottom end of prosthetic valve 20. Frame assembly 22 includes avalve frame 30 (alternatively “inner frame 30”) that includes a tubularportion 32 (alternatively, “inner frame tubular portion 32”) that has anupstream end 34 and a downstream end 36, and is shaped to define a lumen38 through the inner frame tubular portion 32 from the upstream end tothe downstream end. Inner frame tubular portion 32 circumscribes axisax1, and thereby defines lumen 38 along the axis. Inner frame 30 furtherincludes an upstream support portion 40, extending from upstream end 34of inner frame tubular portion 32. Frame assembly 22 further includes atleast one leg 50 (alternatively, “ventricular anchor support 50”),coupled to inner frame 30 at (e.g., via) a coupling point 52, and havinga tissue-engaging flange 54 (alternatively, “ventricular anchoring leg54”).

In some embodiments, and as described hereinbelow, ventricular anchorsupport 50 is part of an outer frame 60, and frames 30 and 60 definerespective coupling elements 31 and 61, which are fixed with respect toeach other at coupling points 52. As illustrated in FIG. 1A, inner frame30 may be positioned at least partially within outer frame 60. In someembodiments, frames 30 and 60 are coupled to each other only at couplingpoints 52 (e.g., only via the fixation of coupling elements 31 and 61with respect to each other).

Prosthetic valve 20 further includes a valve member 58 (e.g., one ormore prosthetic leaflets) disposed within lumen 38, and configured tofacilitate one-way liquid flow through the lumen from upstream end 34 todownstream end 36 (e.g., thereby defining the orientation of theupstream and downstream ends of inner frame tubular portion 32). FIG. 1Ashows prosthetic valve 20 in a fully-expanded state, in which frameassembly 22 is in a fully-expanded state. FIG. 1B shows an exploded viewof frame assembly 22 in its fully-expanded state. FIGS. 2A-E showrespective states of prosthetic valve 20, which will be discussed inmore detail hereinbelow with respect to the implantation of theprosthetic valve and the anatomy in which the prosthetic valve isimplanted. FIG. 2A shows prosthetic valve 20 in a compressed state (inwhich frame assembly 22 is in a compressed state), for percutaneousdelivery of the prosthetic valve to the heart of the subject. In someembodiments, in the compressed state, ventricular anchor support 50(including ventricular anchoring leg 54 thereof) is in a constrained-legstate in which the ventricular anchoring leg is generally parallel withaxis ax1. Further, in the compressed state, upstream support portion 40is generally tubular, collinear with inner frame tubular portion 32(e.g., extending collinearly from the inner frame tubular portion), anddisposed around axis ax1.

FIG. 2B shows a state of prosthetic valve 20 in which ventricularanchoring leg 54 of each ventricular anchor support 50 extends radiallyaway from axis ax1 (e.g., radially away from inner frame tubular portion32). FIG. 2C shows a state of prosthetic valve 20 in whichupstream-support portion 40 extends radially away from axis ax1 (andthereby radially away from inner frame tubular portion 32). FIG. 2Dshows a state of prosthetic valve 20 in which both ventricular anchoringleg 54 and portion 40 extend away from axis ax1. In the fully-expandedstate (FIGS. 1A-B) both upstream support portion 40 and ventricularanchoring leg 54 extend radially away from axis ax1. In someembodiments, frame assembly 22 is biased (e.g., shape-set) to assume itsfully-expanded state, which is shown in FIG. 2E. Transitioning ofprosthetic valve 20 between the respective states may be controlled bydelivery apparatus, such as by constraining the prosthetic valve in acompressed state within a delivery tube and/or against a control rod,and selectively releasing portions of the prosthetic valve to allow themto expand.

In the compressed state of frame assembly 22, inner frame tubularportion 32 has a diameter d1, and in the expanded state, the inner frametubular portion has a diameter d2 that is greater that diameter d1. Insome embodiments, diameter d1 is 4-15 mm, (e.g., 5-11 mm) and diameterd2 is 20-50 mm, (e.g., 23-33 mm). Frame assembly 22 is configured suchthat increasing the diameter of inner frame tubular portion 32 (e.g.,from d1 to d2) causes longitudinal movement of ventricular anchoring leg54 away from coupling point 52. In the same way, reducing the diameterof inner frame tubular portion 32 (e.g., from d2 to d1) causeslongitudinal movement of ventricular anchoring leg 54 toward couplingpoint 52. It is to be noted that the term “longitudinal movement”(including the specification and the claims) means movement parallelwith central longitudinal axis ax1. Therefore longitudinal movement ofventricular anchoring leg 54 away from coupling point 52 meansincreasing a distance, measured parallel with longitudinal axis ax1,between ventricular anchoring leg 54 and coupling point 52. An exampleof such a configuration is described in more detail with respect to FIG.3A.

Thus, expansion of inner frame tubular portion 32 from its compressedstate toward its expanded state (i) increases a circumferential distancebetween each of coupling points 52 and its adjacent coupling points(e.g., between each of outer-frame coupling elements 61 and its adjacentouter-frame coupling elements) (e.g., from d8 to d9), and (ii) movesventricular anchor support 50 in a longitudinally upstream directionwith respect to the inner frame tubular portion.

In some embodiments, frame assembly 22 is configured such thatincreasing the diameter of inner frame tubular portion 32 also causeslongitudinal movement of upstream support portion 40 toward couplingpoint 52, e.g., as described in more detail with respect to FIGS. 3B-C.In some embodiments, frame assembly 22 is configured such thatincreasing the diameter of inner frame tubular portion 32 also causeslongitudinal movement of upstream end 34 of inner frame tubular portion32 toward coupling point 52. In the same way, reducing the diameter ofinner frame tubular portion 32 causes longitudinal movement of upstreamend 34 away from coupling point 52.

In some embodiments, upstream support portion 40 includes a plurality ofatrial anchoring arms 46 that each extends radially outward from innerframe tubular portion 32 (e.g., from upstream end 34 of the inner frametubular portion). Atrial anchoring arms 46 are flexible. In some suchembodiments, atrial anchoring arms 46 are coupled to inner frame tubularportion 32 such that each arm may deflect independently of adjacentatrial anchoring arms 46 during implantation (e.g., due to anatomicaltopography).

In some embodiments, upstream support portion 40 includes a plurality ofbarbs 48 that extend out of a downstream surface of the upstream supportportion. For example, each atrial anchoring arm 46 may include one ormore of barbs 48. Barbs 48 press into tissue upstream of the nativevalve (e.g., into the valve annulus), thereby inhibiting downstreammovement of prosthetic valve 20 (in addition to inhibition of downstreammovement provided by the geometry of upstream support portion 40).

One or more surfaces of frame assembly 22 are covered with a covering23, which may include a flexible sheet, such as a fabric, e.g.,including polyester. In some embodiments, covering 23 covers at leastpart of inner frame tubular portion 32, lining an inner surface of theinner frame tubular portion, and thereby defining lumen 38.

Additionally or alternatively, upstream support portion 40 is coveredwith covering 23, e.g., extending between atrial anchoring arms 46 toform an annular shape. It is hypothesized that this reduces a likelihoodof paravalvular leakage. In such embodiments, excess covering 23 may beprovided between atrial anchoring arms 46 of upstream support portion40, so as to facilitate their independent movement. Although FIG. 1Ashows covering 23 covering an upstream side of upstream support portion40, the covering additionally (or alternatively) covers the downstreamside of the upstream support portion. For example, covering 23 mayextend over the tips of atrial anchoring arms 46 and down the outside ofthe arms, or a separate piece of covering may be provided on thedownstream side of the upstream support portion.

Alternatively, each atrial anchoring arm 46 may be individually coveredin a sleeve of covering 23, thereby facilitating independent movement ofthe arms.

In some embodiments, at least a portion of ventricular anchor support 50(e.g., ventricular anchoring legs 54 thereof) is covered with covering23.

In some embodiments, frame assembly 22 includes a plurality ofventricular anchor supports 50 (e.g., two or more ventricular anchorsupports, e.g., 2-16 ventricular anchor supports, such as 4-12ventricular anchor supports, such as 6-12 ventricular anchor supports),arranged circumferentially around inner frame 30 (e.g., around theoutside of inner frame tubular portion 32). In some embodiments, frameassembly 22 includes a plurality of coupling points 52 at which theventricular anchor supports are coupled to inner frame 30.

As described in more detail hereinbelow (e.g., with reference to FIG.3A), each ventricular anchor support 50 may be coupled to a couplingpoint 52 via a strut 70. In some embodiments, each ventricular anchorsupport 50 is coupled to a plurality of (e.g., two) coupling points 52via a respective plurality of (e.g., two) struts 70. In suchembodiments, frame assembly 22 is arranged such that, in the expandedstate of the frame assembly, ventricular anchor support 50 is disposed,circumferentially with respect to inner frame tubular portion 32,between two struts, and each of the two struts are disposed,circumferentially with respect to the inner frame tubular portion,between the ventricular anchor support and a respective coupling point52.

In some embodiments, a plurality of (e.g., two) ventricular anchorsupports 50 are coupled to each coupling point 52 via a respectiveplurality of (e.g., two) struts 70. In such embodiments, frame assembly22 is arranged such that, in the expanded state of the frame assembly,coupling point 52 is disposed, circumferentially with respect to innerframe tubular portion 32, between two struts 70, and each of the twostruts are disposed, circumferentially with respect to the inner frametubular portion, between the coupling point and a respective ventricularanchor support 50.

In some embodiments, frame assembly 22 includes an outer frame (e.g., aleg frame) 60 that circumscribes inner frame tubular portion 32,includes (or defines) the plurality of ventricular anchoring supports 50and the plurality of struts 70, and is coupled to inner frame 30 at theplurality of coupling points 52, such that the plurality of ventricularanchoring supports are distributed circumferentially around the innerframe tubular portion. In such embodiments, outer frame 60 includes aring 66 that is defined by a pattern of alternating peaks 64 and troughs62, and that circumscribes inner frame tubular portion 32. For example,the ring may include struts 70, extending between the peaks and troughs.Peaks 64 are longitudinally closer to upstream end 34 of inner frametubular portion 32 than to downstream end 36, and troughs 62 arelongitudinally closer to the downstream end than to the upstream end.(It is to be noted that throughout this patent application, includingthe specification and the claims, the term “longitudinally” means withrespect to longitudinal axis ax1. For example, “longitudinally closer”means closer along axis ax1 (whether positioned on axis ax1 or lateralto axis ax1), and “longitudinal movement” means a change in positionalong axis ax1 (which may be in additional to movement toward or awayfrom axis ax1). Therefore, peaks 64 are closer than troughs 62 toupstream end 34, and troughs 62 are closer than peaks 64 to downstreamend 36. As illustrated in FIG. 1B, outer frame 60 may include multiplerings 66; in embodiments depicted in FIG. 1B, outer frame 60 includestwo rings 66 connected by ventricular anchoring supports 50. Rings 66and ventricular anchor supports 50 may form an annular outer frametubular portion 65. Outer frame tubular portion 65 may have an upstreamend 67 (alternatively, “atrial end 67”) and a downstream end 69(alternatively, “ventricular end 69”), and may circumscribe axis ax1. Insome embodiments, upstream end 67 may constitute a portion of the mostupstream ring 66 and downstream end 69 may constitute a portion of themost downstream ring 66. As also illustrated in FIG. 1B, ventricularanchoring legs 54 may extend from outer frame tubular portion 65. Forembodiments in which frame 60 includes ring 66, each ventricular anchorsupport 50 is coupled to the ring (or defined by frame 60) at arespective trough 62.

In the embodiment shown, the peaks and troughs are defined by ring 66having a generally zig-zag shape. However, the scope of the inventionincludes ring 66 having another shape that defines peaks and troughs,such as a serpentine or sinusoid shape.

In some embodiments, inner frame tubular portion 32 and outer frametubular portion 65 may form annular valve body 25. Annular valve body 25may circumscribe axis ax1, and atrial anchoring arms 46 and ventricularanchoring legs 54 may extend from annular valve body 25. Annular valvebody 25 may have an upstream end (alternatively, an “atrial end”), adownstream end (alternatively, a “ventricular end”), and an intermediateportion extending between the upstream end (i.e., the atrial end) anddownstream end (i.e., the ventricular end). For example, in embodimentsdepicted in FIG. 1A, upstream end 34 and downstream end 36 of innerframe tubular portion 32 may constitute the upstream and downstream endsof annular valve body 25, respectively. According to such embodiments,the intermediate portion of annular valve body 25 may include portionsof annular valve body 25 positioned between upstream end 34 anddownstream end 36. However, one of ordinary skill will understand thatthis embodiment is merely exemplary, and that other portions of annularvalve body 25 may form the upstream and downstream ends of annular valvebody 25.

For embodiments in which frame assembly 22 has a plurality of couplingpoints 52, the coupling points (and therefore coupling elements 31 and61) are disposed circumferentially around the frame assembly (e.g.,around axis ax1), in some embodiments on a transverse plane that isorthogonal to axis ax1. This transverse plane is illustrated by theposition of section A-A in FIG. 2B. Alternatively, coupling points 52may be disposed at different longitudinal heights of frame assembly 22,e.g., such that different ventricular anchoring legs 54 are positionedand/or moved differently to others. In some embodiments, coupling points52 (and therefore coupling elements 31 and 61) are disposedlongitudinally between upstream end 24 and downstream end 26 of frameassembly 22, but not at either of these ends. Additionally oralternatively, coupling points 52 are disposed longitudinally betweenupstream end 34 and downstream end 36 of inner frame tubular portion 32,but not at either of these ends. For example, the coupling points may bemore than 3 mm (e.g., 4-10 mm) both from end 34 and from end 36. It ishypothesized that this advantageously positions the coupling points at apart of inner frame tubular portion 32 that is more rigid than end 34 orend 36.

It is to be noted that ventricular anchor support 50 is expandable intoits expanded state (e.g., a released-leg state) such that ventricularanchoring leg 54 extends away from axis ax1, independently of increasingthe diameter of inner frame tubular portion 32 (e.g., as shown in FIGS.2B & 2D). Similarly, upstream support portion 40 is expandable into itsexpanded state (e.g., a released-arm state) such that it (e.g., arms 46thereof) extends away from axis ax1, independently of increasing thediameter of inner frame tubular portion 32 (e.g., as shown in FIGS. 2C &2D). The state shown in FIG. 2D may be considered to be an intermediatestate. Therefore, prosthetic valve 20 is configured such thatventricular anchor supports 50 (e.g., ventricular anchoring legs 54thereof) and upstream support portion 40 are expandable such that theyboth extend away from axis ax1, while retaining a distance d3therebetween. This distance is subsequently reducible to a distance d4by expanding inner frame tubular portion 32 (e.g., shown in FIG. 2E).

In some embodiments, while inner frame tubular portion 32 remains in itscompressed state, leg 54 can extend away from axis ax1 over 40 percent(e.g., 40-80 percent, such as 40-70 percent) of the distance that itextends from the axis subsequent to the expansion of the inner frametubular portion. For example, for embodiments in which prosthetic valve20 includes a leg 54 on opposing sides of the prosthetic valve, a spand15 of the ventricular anchoring legs while inner frame tubular portion32 is in its compressed state may be at least 40 percent (e.g., 40-80percent, such as 40-70 percent) as great as a span d16 of theventricular anchoring legs subsequent to the expansion of the innerframe tubular portion. In some embodiments, span d15 is greater than 15mm and/or less than 50 mm (e.g., 20-30 mm). In some embodiments, spand16 is greater than 30 mm and/or less than 60 mm (e.g., 40-50 mm). It isto be noted that leg 54 is effectively fully expanded, with respect toother portions of ventricular anchor support 50 and/or with respect toinner frame tubular portion 32, before and after the expansion of theinner frame tubular portion.

Similarly, in some embodiments, while inner frame tubular portion 32remains in its compressed state, upstream support portion 40 (e.g., arms46) can extend away from axis ax1 over 30 percent (e.g., 30-70 percent)of the distance that it extends from the axis subsequent to theexpansion of the inner frame tubular portion. That is, in someembodiments, a span d17 of the upstream support portion while innerframe tubular portion 32 is in its compressed state may be at least 30percent (e.g., 30-70 percent) as great as a span d18 of the upstreamsupport portion subsequent to the expansion of the inner frame tubularportion. In some embodiments, span d17 is greater than 16 mm (e.g.,greater than 20 mm) and/or less than 50 mm (e.g., 30-40 mm). In someembodiments, span d18 is greater than 40 mm and/or less than 65 mm(e.g., 45-56 mm, such as 45-50 mm). It is to be noted that upstreamsupport portion 40 is effectively fully expanded, with respect to innerframe tubular portion 32, before and after the expansion of the innerframe tubular portion.

It is to be noted that when inner frame tubular portion 32 is expanded,ventricular anchoring legs 54 translate radially outward from span d15to span d16 (e.g., without deflecting). In some embodiments upstreamsupport portion 40 behaves similarly (e.g., arms 46 translated radiallyoutward from span d17 to span d18, e.g., without deflecting). That is,an orientation of each ventricular anchoring leg 54 and/or each atrialanchoring arm 46 with respect to inner frame tubular portion 32 and/oraxis ax1 is the same in the state shown in FIG. 2D as it is in the stateshown in FIG. 2E. Similarly, in some embodiments an orientation of eachventricular anchoring leg 54 with respect to upstream support portion 40(e.g., with respect to one or more atrial anchoring arms 46 thereof) isthe same before and after expansion of inner frame tubular portion 32.

In some embodiments, increasing the diameter of inner frame tubularportion 32 from d1 to d2 causes greater than 1 mm and/or less than 20 mm(e.g., 1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement ofleg 54 away from coupling point 52. In some embodiments, increasing thediameter of inner frame tubular portion 32 from d1 to d2 causes greaterthan 1 mm and/or less than 20 mm (e.g., 1-20 mm, such as 1-10 mm or 5-20mm) of longitudinal movement of upstream support portion 40 towardcoupling point 52. In some embodiments, distance d3 is 7-30 mm. For someembodiments, distance d4 is 0-15 mm (e.g., 2-15 mm). In someembodiments, increasing the diameter of inner frame tubular portion 32from d1 to d2 reduces the distance between the upstream support portionand legs 54 by more than 5 mm and/or less than 30 mm, such as 5-30 mm(e.g., 10-30 mm, such as 10-20 mm or 20-30 mm). In some embodiments, thedifference between d3 and d4 is generally equal to the differencebetween d1 and d2. In some embodiments, the difference between d3 and d4is more than 1.2 and/or less than 3 times (e.g., 1.5-2.5 times, such asabout 2 times) greater than the difference between d1 and d2.

In some embodiments, ventricular anchoring legs 54 curve such that a tipof each leg 54 is disposed at a shallower angle with respect to innerregion 42 of upstream support portion 40, than are portions ofventricular anchor support 50 that are closer to downstream end 26 offrame assembly 22. In such embodiments, a tip of each ventricularanchoring leg may be generally parallel with inner region 42. In suchembodiments, while inner frame tubular portion 32 is in its expandedstate, a tip portion 55 of each ventricular anchoring leg 54 thatextends from the tip of the leg at least 2 mm along the ventricularanchoring leg, is disposed within 2 mm of upstream support portion 40.Thus, in some embodiments, while inner frame tubular portion 32 is inits expanded state, for at least 5 percent (e.g., 5-8 percent, or atleast 8 percent) of span 18 of upstream support portion 40, the upstreamsupport portion is disposed within 2 mm of a leg 54.

In some embodiments, in the absence of any obstruction (such as tissueof the valve or covering 23) between leg 54 and upstream support portion40, increasing the diameter of inner frame tubular portion 32 from d1 tod2 causes the ventricular anchoring leg 54 and the upstream supportportion to move past each other (e.g., the ventricular anchoring leg 54may move between arms 46 of the upstream support portion), such that theventricular anchoring leg 54 is closer to the upstream end of prostheticvalve 20 than is the upstream support portion, e.g., as shownhereinbelow for frame assemblies 122 and 222, mutatis mutandis. (Forembodiments in which upstream support portion 40 is covered by covering23, legs 54 do not pass the covering. For example, in the absence of anyobstruction, legs 54 may pass between arms 46, and press directlyagainst covering 23.) It is hypothesized that in some embodiments thisconfiguration applies greater force to the valve tissue beingsandwiched, and thereby further facilitates anchoring of the prostheticvalve. That is, in some embodiments, distance d3 is smaller than the sumof distance d5 and a distance d14 (described with reference to FIG. 3C).In some embodiments, increasing the diameter of inner frame tubularportion 32 from d1 to d2 advantageously causes legs 54 and upstreamsupport portion 40 to move greater than 3 mm and/or less than 25 mm(e.g., greater than 5 mm and/or less than 15 mm, e.g., 5-10 mm, such asabout 7 mm) with respect to each other (e.g., toward each other and thenpast each other).

In some embodiments, in the expanded state of frame assembly 22,upstream support portion 40 has an inner region (e.g., an inner ring) 42that extends radially outward at a first angle with respect to axis ax1(and with respect to inner frame tubular portion 32), and an outerregion (e.g., an outer ring) 44 that extends, from the inner region,further radially outward from the inner frame tubular portion at asecond angle with respect to the inner frame tubular portion, the secondangle being smaller than the first angle. For example, in someembodiments inner region 42 extends radially outward at an angle alpha_1of 60-120 degrees (e.g., 70-110 degrees) with respect to axis ax1, andouter region 44 extends radially outward at an angle alpha_2 of 5-70degrees (e.g., 10-60 degrees) with respect to axis ax1.

It is to be noted that angles alpha_1 and alpha_2 are measured betweenthe respective region support portion 40, and the portion of axis ax1that extends in an upstream direction from the level of frame assembly22 at which the respective region begins to extend radially outward.

In some embodiments in which prosthetic valve 20 is configured to beplaced at an atrioventricular valve (e.g., a mitral valve or a tricuspidvalve) of the subject, region 42 is configured to be placed against theupstream surface of the annulus of the atrioventricular valve, andregion 44 is configured to be placed against the walls of the atriumupstream of the valve.

In some embodiments, outer region 44 is more flexible than inner region42. For example, and as shown, each arm 46 may have a differentstructure in region 44 than in region 42. It is hypothesized that therelative rigidity of region 42 provides resistance against ventricularmigration of prosthetic valve 20, while the relative flexibility ofregion 44 facilitates conformation of upstream support portion 40 to theatrial anatomy.

In some embodiments, two or more of arms 46 are connected by a connector(not shown), reducing the flexibility, and/or the independence ofmovement of the connected arms relative to each other. In someembodiments, arms 46 are connected in particular sectors of upstreamsupport portion 40, thereby making these sectors more rigid than sectorsin which the arms are not connected. For example, a relatively rigidsector may be provided to be placed against the posterior portion of themitral annulus, and a relatively flexible sector may be provided to beplaced against the anterior side of the mitral annulus, so as to reduceforces applied by upstream support portion 40 on the aortic sinus.

In some embodiments, and as shown, coupling points 52 are disposedcloser to downstream end 26 of frame assembly 22 than are ventricularanchoring legs 54, or is upstream support portion 40.

As described in more detail with respect to FIGS. 4A-F, the movement ofventricular anchoring leg 54 away from coupling point 52 (and themovement of upstream support portion 40 toward the coupling point)facilitates the sandwiching of tissue of the native valve (e.g., leafletand/or annulus tissue) between the ventricular anchoring leg 54 and theupstream support portion, thereby securing prosthetic valve 20 at thenative valve.

In some embodiments, in the compressed state of inner frame tubularportion 32, a downstream end of each ventricular anchor support 50 islongitudinally closer than valve-frame coupling elements 31 todownstream end 36, and ventricular anchoring leg 54 of each ventricularanchor support 50 is disposed longitudinally closer than the valve-framecoupling elements to upstream end 34. In some embodiments, this is alsothe case in the expanded state of inner frame tubular portion 32.

FIGS. 3A-C show structural changes in frame assembly 22 duringtransitioning of the assembly between its compressed and expandedstates, in accordance with some embodiments of the invention. FIGS. 3A-Ceach show a portion of the frame assembly, the structural changesthereof being representative of the structural changes that occur inother portions of the frame assembly. FIG. 3A shows a ventricular anchorsupport 50 and struts 70 (e.g., a portion of outer frame 60), andillustrates the structural changes that occur around outer frame 60.FIG. 3B shows a portion of inner frame 30, and illustrates thestructural changes that occur around the inner frame. FIG. 3C showsinner frame 30 as a whole. In each of FIGS. 3A-C, state (A) illustratesthe structure while frame assembly 22 (and in particular inner frametubular portion 32) is in its compressed state, and state (B)illustrates the structure while the frame assembly (and in particularinner frame tubular portion 32) is in its expanded state.

FIG. 3A shows structural changes in the coupling of ventricularanchoring supports 50 to coupling point 52 (e.g., structural changes ofouter frame 60) during the transitioning of frame assembly 22 (and inparticular inner frame tubular portion 32) between its compressed andexpanded states. Each ventricular anchor support 50 is coupled to innerframe 30 via at least one strut 70, which connects the ventricularanchoring support to coupling point 52. In some embodiments, eachventricular anchor support 50 is coupled to inner frame 30 via aplurality of struts 70. A first end 72 of each strut 70 is coupled toventricular anchor support 50, and a second end 74 of each strut iscoupled to a coupling point 52. As described hereinabove, forembodiments in which frame 60 includes ring 66, each ventricular anchorsupport 50 is coupled to the ring at a respective trough 62. Ring 66 mayinclude struts 70, extending between the peaks and troughs, with eachfirst end 72 at (or close to) a trough 62, and each second end 74 at (orclose to) a peak 64.

In the compressed state of frame assembly 22 (and in particular of innerframe tubular portion 32), each strut 70 is disposed at a first angle inwhich first end 72 is disposed closer than second end 74 to thedownstream end of the frame assembly. Expansion of frame assembly 22(and in particular of inner frame tubular portion 32) toward itsexpanded state causes strut 70 to deflect to a second angle. Thisdeflection moves first end 72 away from the downstream end of frameassembly 22. That is, in the expanded state of frame assembly 22, firstend 72 is further from the downstream end of the frame assembly than itis when the frame assembly is in its compressed state. This movement isshown as a distance d5 between the position of end 72 in state (A) andits position in state (B). This movement causes the above-describedmovement of ventricular anchoring legs 54 away from coupling points 52.As shown, ventricular anchoring legs 54 move the same distance d5 inresponse to expansion of frame assembly 22.

For embodiments in which outer frame 60 includes ring 66, the pattern ofalternating peaks and troughs may be described as having an amplitudelongitudinally between the peaks and troughs, i.e., measured parallelwith central longitudinal axis ax1 of frame assembly 22, and thetransition between the compressed and expanded states may be describedas follows: In the compressed state of frame assembly 22 (and inparticular of inner frame tubular portion 32), the pattern of ring 66has an amplitude d20. In the expanded state frame assembly 22 (and inparticular of inner frame tubular portion 32), the pattern of ring 66has an amplitude d21 that is lower than amplitude d20. Because (i) it isat peaks 64 that ring 66 is coupled to inner frame 30 at coupling points52, and (ii) it is at troughs 62 that ring 66 is coupled to ventricularanchoring supports 50, this reduction in the amplitude of the pattern ofring 66 moves ventricular anchoring supports 50 (e.g., ventricularanchoring legs 54 thereof) longitudinally further from the downstreamend of the frame assembly. The magnitude of this longitudinal movement(e.g., the difference between magnitudes d20 and d21) is equal to d5.

In some embodiments, distance d5 is the same distance as the distancethat ventricular anchoring leg 54 moves away from coupling point 52during expansion of the frame assembly. That is, a distance betweenventricular anchoring leg 54 and the portion of ventricular anchorsupport 50 that is coupled to strut 70, remains constant duringexpansion of the frame assembly. In some embodiments, the longitudinalmovement of ventricular anchoring leg 54 away from coupling point 52 isa translational movement (e.g., a movement that does not includerotation or deflection of the ventricular anchoring leg 54).

In some embodiments, a distance d6, measured parallel to axis ax1 offrame assembly 22, between coupling point 52 and first end 72 of strut70 while assembly 22 is in its compressed state, is 3-15 mm. In someembodiments, a distance d7, measured parallel to axis ax1, betweencoupling point 52 and first end 72 of strut 70 while assembly 22 is inits expanded state, is 1-5 mm (e.g., 1-4 mm).

In some embodiments, amplitude d20 is 2-10 mm (e.g., 4-7 mm). In someembodiments, amplitude d21 is 4-9 mm (e.g., 5-7 mm).

In some embodiments, and as shown, in the expanded state, first end 72of strut 70 is disposed closer to the downstream end of frame assembly22 than is coupling point 52. In some embodiments, in the expandedstate, first end 72 of strut 70 is disposed further from the downstreamend of frame assembly 22 than is coupling point 52.

For embodiments in which frame assembly 22 includes a plurality ofventricular anchoring supports 50 and a plurality of coupling points 52(e.g., for embodiments in which the frame assembly includes outer frame60) expansion of the frame assembly increases a circumferential distancebetween adjacent coupling points 52, and an increase in acircumferential distance between adjacent ventricular anchoring supports50. FIG. 3A shows such an increase in the circumferential distancebetween adjacent coupling points 52, from a circumferential distance d8in the compressed state to a circumferential distance d9 in the expandedstate. In some embodiments, distance d8 is 1-6 mm. In some embodiments,distance d9 is 3-15 mm.

In some embodiments, in addition to being coupled via ring 66 (e.g.,struts 70 thereof) ventricular anchoring supports 50 are also connectedto each other via connectors 78. Connectors 78 allow the describedmovement of ventricular anchoring supports 50 during expansion of frameassembly 22, but stabilize ventricular anchoring supports 50 relative toeach other while the frame assembly is in its expanded state. Forexample, connectors 78 may bend and/or deflect during expansion of theframe assembly.

FIGS. 3B-C show structural changes in inner frame 30 during thetransitioning of frame assembly 22 between its compressed and expandedstates. Inner frame tubular portion 32 of inner frame 30 is defined by aplurality of cells 80, which are defined by the repeating pattern of theinner frame. When frame assembly 22 is expanded from its compressedstate toward its expanded state, cells 80 (i) widen from a width d1 to awidth d11 (measured orthogonal to axis ax1 of the frame assembly), and(ii) shorten from a height d12 to a height d13 (measured parallel toaxis ax1 of the frame assembly). This shortening reduces the overallheight (i.e., a longitudinal length between upstream end 34 anddownstream end 36) of inner frame tubular portion 32 from a height d22to a height d23, and thereby causes the above-described longitudinalmovement of upstream support portion 40 toward coupling points 52 by adistance d14 (shown in FIG. 3C). For some embodiments, and as shown,coupling points 52 are disposed at the widest part of each cell.

Due to the configurations described herein, the distance by whichventricular anchoring legs 54 move with respect to (e.g., toward, ortoward-and-beyond) upstream support portion 40 (e.g., arms 46 thereof),is greater than the reduction in the overall height of inner frametubular portion 32 (e.g., more than 20 percent greater, such as morethan 30 percent greater, such as more than 40 percent greater). That is,prosthetic valve 20 includes an inner frame (30) that includes an innerframe tubular portion (32) that circumscribes a longitudinal axis (ax1)of the inner frame so as to define a lumen (38) along the axis, theinner frame tubular portion having an upstream end (34), a downstreamend (36), a longitudinal length therebetween, and a diameter (e.g., d1or d2) transverse to the longitudinal axis; a valve member (58), coupledto the inner frame tubular portion, disposed within the lumen, andarranged to provide unidirectional upstream-to-downstream flow of bloodthrough the lumen; an upstream support portion (40), coupled to theinner frame tubular portion; and an outer frame (60), coupled to theinner frame tubular portion, and including a ventricular anchoring leg(54), wherein the prosthetic valve has a first state (e.g., as shown inFIG. 2D and FIG. 4D) and a second state (e.g., as shown in FIG. 2E andFIG. 4E), in both the first state and the second state, (i) the upstreamsupport portion extends radially outward from the inner frame tubularportion, and (ii) the ventricular anchoring leg 54 extends radiallyoutward from the inner frame tubular portion, and the inner frametubular portion, the upstream support portion, and the outer frame arearranged such that transitioning of the prosthetic valve from the firststate toward the second state increases the diameter of the inner frametubular portion by a diameter-increase amount (e.g., the differencebetween d1 and d2), decreases the length of the inner frame tubularportion by a length-decrease amount (e.g., the difference between d22and d23), and moves the ventricular anchoring leg 54 a longitudinaldistance with respect to (e.g., toward or toward-and-beyond) theupstream support portion (e.g., the difference between d3 and d4), thisdistance being greater than the length-decrease amount.

As shown in the figures, inner frame 30 is coupled to outer frame 60 bycoupling between (i) a valve-frame coupling element 31 defined by innerframe 30, and (ii) an outer-frame coupling element 61 defined by outerframe 60 (e.g., an outer-frame coupling element is coupled to end 74 ofeach strut). In some embodiments, elements 31 and 61 are fixed withrespect to each other. Each coupling point 52 is thereby defined as thepoint at which a valve-frame coupling element and a correspondingouter-frame coupling element 61 are coupled (e.g., are fixed withrespect to each other). In some embodiments, and as shown, elements 31and 61 are eyelets configured to be coupled together by a connector,such as a pin or suture. In some embodiments, elements 31 and 61 aresoldered or welded together.

In some embodiments, and as shown, valve-frame coupling elements 31 aredefined by inner frame tubular portion 32, and are disposedcircumferentially around central longitudinal axis ax1. Outer-framecoupling elements 61 are coupled to ring 66 (or defined by frame 60,such as by ring 66) at respective peaks 64.

As shown (e.g., in FIGS. 2A-E), inner frame 30 (e.g., inner frametubular portion 32 thereof) and outer frame 60 (e.g., ring 66 thereof)are arranged in a close-fitting coaxial arrangement, in both theexpanded and compressed states of frame assembly 22. Ignoring spaces dueto the cellular structure of the frames, a radial gap d19 between innerframe 30 (e.g., inner frame tubular portion 32 thereof) and outer frame60 (e.g., ring 66 thereof) may be less than 2 mm (e.g., less than 1 mm),in both the compressed and expanded states, and during the transitiontherebetween. This is facilitated by the coupling between frames 30 and60, and the behavior, described hereinabove, of frame 60 in response tochanges in the diameter of inner frame tubular portion 32 (e.g., ratherthan solely due to delivery techniques and/or tools). In someembodiments, more than 50 percent (e.g., more than 60 percent) of ring66 is disposed within 2 mm of inner frame tubular portion 32 in both thecompressed and expanded states, and during the transition therebetween.In some embodiments, more than 50 percent (e.g., more than 60 percent)of outer frame 60, except for ventricular anchoring legs 54, is disposedwithin 2 mm of inner frame tubular portion 32 in both the compressed andexpanded states, and during the transition therebetween.

The structural changes to frame assembly 22 (e.g., to outer frame 60thereof) are described hereinabove as they occur during (e.g., as aresult of) expansion of the frame assembly (in particular inner frametubular portion 32 thereof). This is the natural way to describe thesechanges because, as described hereinbelow with respect to FIGS. 4A-6,assembly 22 is in its compressed state during percutaneous delivery tothe prosthetic valve site, and is subsequently expanded. However, thenature of prosthetic valve 20 may be further understood by describingstructural changes that occur during compression of the frame assembly(e.g., a transition from the expanded state in FIG. 2E to theintermediate state in FIG. 2D), in particular inner frame tubularportion 32 thereof (including if inner frame tubular portion 32 werecompressed by application of compressive force to the inner frametubular portion, and not to frame 60 except via the inner frame tubularportion pulling frame 60 radially inward). Such descriptions may also berelevant because prosthetic valve 20 is compressed (i.e., “crimped”)soon before its percutaneous delivery, and therefore these changes mayoccur while prosthetic valve 20 is in the care of the operatingphysician.

In some embodiments, the fixation of peaks 64 to respective sites ofinner frame tubular portion 32 is such that compression of the innerframe tubular portion from its expanded state toward its compressedstate such that the respective sites of the inner frame tubular portionpull the peaks radially inward via radially-inward tension on couplingpoints 52: (i) reduces a circumferential distance between each of thecoupling points and its adjacent coupling points (e.g., from d9 to d8),and (ii) increases the amplitude of the pattern of ring 66 (e.g., fromd21 to d20).

In some embodiments, the fixation of outer-frame coupling elements 61 tovalve-frame coupling elements 31 is such that compression of inner frametubular portion 32 from its expanded state toward its compressed statesuch that the valve-frame coupling elements pull the outer-framecoupling elements radially inward: (i) reduces a circumferentialdistance between each of the outer-frame coupling elements and itsadjacent outer-frame coupling elements (e.g., from d9 to d8), and (ii)increases the amplitude of the pattern of ring 66 (e.g., from d21 tod20).

In some embodiments, the fixation of peaks 64 to the respective sites ofinner frame tubular portion 32 is such that compression of the innerframe tubular portion from its expanded state toward its compressedstate (i) pulls the peaks radially inward via radially-inward pulling ofthe respective sites of the inner frame tubular portion on the peaks,(ii) reduces a circumferential distance between each of coupling points52 and its adjacent coupling points (e.g., from d9 to d8), and (iii)increases the amplitude of the pattern of ring 66 (e.g., from d21 tod20), without increasing radial gap d19 between inner frame 30 (e.g.,inner frame tubular portion 32 thereof) and the ring by more than 1.5mm.

In some embodiments, the fixation of outer-frame coupling elements 61with respect to valve-frame coupling elements 31 is such thatcompression of inner frame tubular portion 32 from its expanded statetoward its compressed state (i) pulls outer-frame coupling elements 61radially inward via radially-inward pulling of valve-frame couplingelements 31 on outer-frame coupling elements 61, (ii) reduces acircumferential distance between each of the outer-frame couplingelements and its adjacent outer-frame coupling elements (e.g., from d9to d8), and (iii) increases the amplitude of the pattern of ring 66(e.g., from d21 to d20), without increasing radial gap d19 between innerframe 30 (e.g., inner frame tubular portion 32 thereof) and the ring bymore than 1.5 mm.

Reference is made to FIGS. 4A-F, which are schematic illustrations ofimplantation of prosthetic valve 20 at a native valve 10 of a heart 4 ofa subject, in accordance with some embodiments of the invention. Valve10 is shown as a mitral valve of the subject, disposed between a leftatrium 6 and a left ventricle 8 of the subject. However prosthetic valve20 may be implanted at another heart valve of the subject, mutatismutandis. Similarly, although FIGS. 4A-F show prosthetic valve 20 beingdelivered transseptally via a sheath 88, the prosthetic valve mayalternatively be delivered by any other suitable route, such astransatrially, or transapically.

Prosthetic valve 20 is delivered, in its compressed state, to nativevalve 10 using a delivery tool 89 that is operable from outside thesubject (FIG. 4A). In some embodiments, prosthetic valve 20 is deliveredwithin a delivery capsule 90 of tool 89, which retains the prostheticvalve in its compressed state. A transseptal approach, such as atransfemoral approach, is shown. In some embodiments, prosthetic valve20 is positioned such that at least ventricular anchoring legs 54 aredisposed downstream of the native valve (i.e., within ventricle 8). Atthis stage, frame assembly 22 of prosthetic valve 20 is as shown in FIG.2A.

Subsequently, ventricular anchoring legs 54 are allowed to protruderadially outward, as described hereinabove, e.g., by releasing them fromcapsule 90 (FIG. 4B). For example, and as shown, capsule 90 may includea distal capsule-portion 92 and a proximal capsule-portion 94, and thedistal capsule-portion may be moved distally with respect to prostheticvalve 20, so as to expose ventricular anchoring legs 54. At this stage,frame assembly 22 of prosthetic valve 20 is as shown in FIG. 2B.

Subsequently, prosthetic valve 20 is moved upstream, such that upstreamsupport portion 40, in its compressed state, is disposed upstream ofleaflets 12 (i.e., within atrium 6). For some embodiments, the upstreammovement of prosthetic valve 20 causes ventricular anchoring legs 54 toengage leaflets 12. However, because of the relatively large distance d3provided by prosthetic valve 20 (described hereinabove), in someembodiments it may not be necessary to move the prosthetic valve so farupstream that ventricular anchoring legs 54 tightly engage leaflets 12and/or pull the leaflets upstream of the valve annulus. Upstream supportportion 40 is then allowed to expand such that it protrudes radiallyoutward, as described hereinabove, e.g., by releasing it from capsule 90(FIG. 4D). For example, and as shown, proximal capsule-portion 94 may bemoved proximally with respect to prosthetic valve 20, so as to exposeupstream support portion 40. At this stage, frame assembly 22 ofprosthetic valve 20 is as shown in FIG. 2D, in which: (i) distance d3exists between upstream support portion 40 and ventricular anchoringlegs 54, (ii) the ventricular anchoring legs have span d15, (iii) theupstream support portion has span d17, and (iv) inner frame tubularportion 32 has diameter d1.

In some embodiments, expansion of frame assembly 22 is inhibited bydistal capsule-portion 92 (e.g., by inhibiting expansion of inner frametubular portion 32), and/or by another portion of delivery tool 89(e.g., a portion of the delivery tool that is disposed within lumen 38).

Subsequently, prosthetic valve 20 is allowed to expand toward itsexpanded state, such that inner frame tubular portion 32 widens todiameter d2, and the distance between upstream support portion 40 andventricular anchoring legs 54 reduces to distance d4 (FIG. 4E). Thissandwiches tissue of valve 10 (including annular tissue and/or leaflets12) between upstream support portion 40 and ventricular anchoring legs54, thereby securing prosthetic valve 20 at the valve. FIG. 4F showsdelivery capsule 90 having been removed from the body of the subject,leaving prosthetic valve 20 in place at valve 10.

As described hereinabove, prosthetic valve 20 is configured such thatwhen inner frame tubular portion 32 is expanded, ventricular anchoringlegs 54 and upstream support portion 40 move a relatively large distancetoward each other. This enables distance d3 to be relatively large,while distance d4 is sufficiently small to provide effective anchoring.As also described hereinabove, prosthetic valve 20 is configured suchthat ventricular anchoring legs 54 and upstream support portion 40 canextend radially outward a relatively large distance while inner frametubular portion 32 remains compressed. It is hypothesized that in someembodiments, these configurations (independently and/or together)facilitate effective anchoring of prosthetic valve 20, by facilitatingplacement of a relatively large proportion of valve tissue (e.g.,leaflets 12) between the ventricular anchoring legs 54 and the upstreamsupport portion prior to expanding inner frame tubular portion 32 andsandwiching the valve tissue.

It is further hypothesized that the relatively great radially-outwardextension of ventricular anchoring legs 54 and upstream support portion40 prior to expansion of inner frame tubular portion 32, furtherfacilitates the anchoring/sandwiching step by reducing radially-outwardpushing of the valve tissue (e.g., leaflets 12) during the expansion ofthe inner frame tubular portion, and thereby increasing the amount ofvalve tissue that is sandwiched.

It is yet further hypothesized that this configuration of prostheticvalve 20 facilitates identifying correct positioning of the prostheticvalve (i.e., with upstream support portion 40 upstream of leaflets 12and ventricular anchoring legs 54 downstream of the leaflets) prior toexpanding inner frame tubular portion 32 and sandwiching the valvetissue.

As shown in FIG. 1A, in some embodiments, in the expanded state of frameassembly 22, prosthetic valve 20 defines a toroidal space 49 betweenventricular anchoring legs 54 and upstream support portion 40 (e.g., aspace that is wider than distance d4). For example, space 49 may have agenerally triangular cross-section. It is hypothesized that in suchembodiments, in addition to sandwiching tissue of the native valvebetween upstream support portion 40 and ventricular anchoring legs 54(e.g., the tips of the legs), space 49 advantageously promotes tissuegrowth therewithin (e.g., between leaflet tissue and covering 23), whichover time further secures prosthetic valve 20 within the native valve.

Reference is now made to FIG. 5, which is a schematic illustration of astep in the implantation of prosthetic valve 20, in accordance with someembodiments of the invention. Whereas FIGS. 4A-F show an implantationtechnique in which ventricular anchoring legs 54 are expanded prior toupstream support portion 40, in some embodiments the upstream supportportion is expanded prior to the ventricular anchoring legs 54. FIG. 5shows a step in such an embodiment.

Reference is again made to FIGS. 2A-5. As noted hereinabove, prostheticvalve 20 may be implanted by causing ventricular anchoring legs 54 toradially protrude before causing upstream support portion 40 to radiallyprotrude, or may be implanted by causing the upstream support portion toprotrude before causing the ventricular anchoring legs 54 to protrude.In some embodiments, prosthetic valve 20 is thereby configured to bedeliverable in a downstream direction (e.g., transseptally, as shown, ortransapically) or in an upstream direction (e.g., transapically or viathe aortic valve). Thus, in some embodiments, an operating physician maydecide which delivery route is preferable for a given application (e.g.,for a given subject, and/or based on available equipment and/orexpertise), and prosthetic valve 20 is responsively prepared for thechosen delivery route (e.g., by loading the prosthetic valve into anappropriate delivery tool).

It is to be noted that in some embodiments, downstream delivery ofprosthetic valve 20 may be performed by expanding ventricular anchoringlegs 54 first (e.g., as shown in FIGS. 4A-F) or by expanding upstreamsupport portion 40 first (e.g., as shown in FIG. 5). Similarly, in someembodiments upstream delivery of prosthetic valve 20 may be performed byupstream support portion 40 first, or by expanding ventricular anchoringlegs 54 first.

Reference is now made to FIG. 6, which is a schematic illustration ofprosthetic valve 20, in the state and position shown in FIG. 4D, inaccordance with some embodiments of the invention. In some embodiments,while prosthetic valve 20 is in the state and position shown in FIG. 4D,leaflets 12 of valve 10 are able to move, at least in part in responseto beating of the heart. Frame (A) shows leaflets 12 during ventricularsystole, and frame (B) shows the leaflets during ventricular diastole.In such embodiments, blood is thereby able to flow from atrium 6 toventricle 8, between leaflets 12 and prosthetic valve 20. It ishypothesized that this advantageously facilitates a more relaxedimplantation procedure, e.g., facilitating retaining of prosthetic valve20 in this state and position for a duration of greater than 8 minutes.During this time, imaging techniques may be used to verify the positionof prosthetic valve 20, and/or positioning of leaflets 12 betweenupstream support portion 40 and legs 54.

Reference is made to FIGS. 7A-B and 8A-B, which are schematicillustrations of frame assemblies 122 and 222 of respective prostheticvalves, in accordance with some embodiments of the invention. Exceptwhere noted otherwise, frame assemblies 122 and 222 are identical toframe assembly 22, mutatis mutandis. Elements of frame assemblies 122and 222 share the name of corresponding elements of frame assembly 22.Additionally, except where noted otherwise, the prosthetic valves towhich frame assemblies 122 and 222 belong are similar to prostheticvalve 20, mutatis mutandis.

Frame assembly 122 includes an inner frame 130 that includes an innerframe tubular portion 132 having an upstream end 134 (alternatively,“atrial end 134”) and a downstream end 136 (alternatively, “ventricularend 136”). Inner frame tubular portion 132 may also include an upstreamsupport portion 140 that may include a plurality of atrial anchoringarms 146. As illustrated in FIG. 7B, atrial anchoring arms 146 mayconnect with the inner frame tubular portion 132 at connection locations141, and may extend from inner frame tubular portion 132 in a generallyradially outward direction to terminal arm ends 147. Atrial anchoringarms 146 may include first portions 145, second portions 142, and thirdportions 144. As shown in FIG. 7B, first portions 145 and third portions144 may extend towards an atrium (i.e., upwards in FIG. 7B) whenprosthetic valve 120 is in an expanded state, while second portions 142may extend towards a ventricle (i.e., downwards in FIG. 7B) whenprosthetic valve 120 is in an expanded state. First portions 145 may bethe inner-most portions of atrial anchoring arms 146 and may connect toinner frame tubular portion 132 at connection locations 141. Frameassembly 122 may also include an outer frame 160 that circumscribes theinner frame, and which includes an outer frame tubular portion 165having an upstream end 167 (alternatively, “atrial end 167”) and adownstream end 169 (alternatively, “ventricular end 169”). Outer frame160 may also include a plurality of ventricular anchoring supports 150that each may include a ventricular anchoring leg 154. Ventricularanchoring legs 154 may connect with the outer frame tubular portion 165at connection locations 157, and may extend from the outer frame tubularportion 165 to respective terminal leg ends 155. As depicted in FIGS. 7Aand 7B, the entire length of the ventricular anchoring legs 154 mayextend towards an atrium when prosthetic valve 120 is implanted in anative mitral valve (i.e., the entire length of legs 154 extend upwardsin FIGS. 7A and 7B). The expression “the entire length of theventricular anchoring legs” may refer to the portions of legs 154between connection locations 157 and terminal ends 155. In someembodiments, outer frame 160 includes a ring 166 to which ventricularanchoring supports 150 are coupled. As illustrated in FIG. 7A,ventricular anchoring supports 150 may be positioned substantiallyparallel to axis ax1 when prosthetic valve 120 is in a constrainedstate. Ring 166 is defined by a pattern of alternating peaks andtroughs, the peaks being fixed to frame 130 at respective couplingpoints 152, e.g., as described hereinabove for frame assembly 22,mutatis mutandis. Rings 166 and ventricular anchor supports 150 may formouter frame tubular portion 165, from which ventricular anchoring legs154 may extend in a generally radially outward direction (as illustratedin FIG. 7B). According to embodiments depicted in FIG. 7B, atrialanchoring arms 146 may be configured to extend radially outward beyondterminal ends 155 of the ventricular anchoring legs 154.

As depicted in FIGS. 7A and 7B, inner frame tubular portion 132 andouter frame tubular portion 165 may form annular valve body 125. Annularvalve body 125 may circumscribe axis ax1, and atrial anchoring arms 146and ventricular anchoring legs 154 may extend from annular valve body125. As depicted in FIG. 7B, upstream end 134 of inner frame tubularportion 132 may form the upstream end (i.e., the atrial end) of annularvalve body 125. Additionally or alternatively, and as also depicted inFIG. 7B, downstream end 136 of the inner frame tubular portion 132 anddownstream end 169 of the outer frame tubular portion 165 may togetherform the downstream end (i.e., the ventricular end) of annular valvebody 125. This may occur because respective downstream ends 136 and 169may be substantially even (i.e., substantially aligned in a commonlateral plane extending along the bottom of frame assembly 122) asillustrated in FIG. 7B. Because the downstream ends of the inner andouter frames are substantially aligned and the upstream end 134 of theinner frame 130 extends in an upstream direction beyond the upstream end167 of the inner frame 130, the inner frame 130 may have a greater axiallength, relative to axis ax1, than outer frame 160. Annular valve body125 may also include an intermediate portion, which may include portionsof annular valve body 125 positioned between the upstream end (atrialend) and downstream end (ventricular end) of the annular valve body 125.Thus, as illustrated in FIG. 7B, atrial anchoring arms 146 andventricular anchoring legs 154 may extend from the intermediate portionof annular valve body 125 in a generally radially outward direction. Asis also illustrated in FIG. 7B, connection locations 141 and 157 may bepositioned within the intermediate portion of annular valve 125.

As depicted in FIG. 7B, inner frame tubular portion 132 may beconstructed of struts intersecting at junctions and forming closedcells. For example, struts 133 may intersect at junctions 137, which mayform the upstream end 134 of the inner frame tubular portion 132. Thus,junctions 137 may also form the upstream end (i.e., the atrial end) ofannular valve body 125. Struts 133 and atrial anchoring arms 146 mayintersect at connection locations 141; in this way, connection locations141 may also be junctions. Inner frame tubular portion 132 may alsoinclude struts 143 intersecting at junctions 139. Similarly, and as alsodepicted in FIG. 7B, outer frame tubular portion 165 may be constructedof struts intersecting at junctions and forming closed cells. Forexample, struts 178 may intersect with ventricular anchoring legs 154 atconnection locations 157; in this way, connection locations 157 may alsobe junctions. Outer frame tubular portion 165 may also include struts170 intersecting with ventricular anchoring supports 150 at junctions163. In some embodiments, closed cells of the inner frame 130 may have adifferent shape than closed cells of the outer frame 160. For example,and as depicted in FIG. 7B, closed cells of the inner frame 130 may havea diamond shape, while closed cells of the outer frame 160 may have achevron shape.

Since junctions 137 are situated along the upstream end (i.e., theatrial end) of annular valve body 125, junctions 137 may be consideredatrial junctions of annular valve body 125. Junctions 139 may besituated along the downstream end 136 of the inner frame tubular portion132, while junctions 163 may be situated along the downstream end 169 ofouter frame tubular portion 165. Thus, junctions 139 and 163 may beconsidered ventricular junctions of annular valve body 125, as both aresituated along the downstream end (that is, the ventricular end) ofannular valve body 125. Thus, the intermediate portion of annular valvebody 125 may include the portions of annular valve body 125 positionedbetween atrial junctions 137 and ventricular junctions 139, 163. Theintermediate portion of annular valve body 125 may include junctions(“intermediate junctions”). For example, and as illustrated in FIG. 7B,junctions 141 and 157 (i.e., connection locations 141 and 157) may besituated within the intermediate portion. Since connection locations141, 157 are junctions, they may constitute intermediate junctions.

As illustrated in FIG. 7B, intermediate junctions 157 (connectionlocations 157) and ventricular anchoring legs 154 may be angularlyaligned with ventricular junctions 163. Ventricular anchoring supports150 may extend between ventricular junctions 163 and intermediatejunctions 157; thus, ventricular anchoring supports 150 may act asstruts. Accordingly, and as illustrated in FIG. 7B, intermediatejunctions 157, to which ventricular anchoring legs 154 are connected,may be junctions at which three struts intersect (two struts 178 andventricular anchoring support 150 intersect at a given intermediatejunction 157). Moreover, and as also illustrated in FIG. 7B, annularvalve body 125 may be configured such that an area between intermediatejunctions 141 and intermediate junctions 157 may be devoid of junctions,as may an area between intermediate junctions 141 and atrial junctions137.

Frame assembly 222 includes an inner frame 230 that includes an innerframe tubular portion 232 and an upstream support portion 240 that mayinclude a plurality of atrial anchoring arms 246, and (ii) an outerframe (e.g., a leg frame) 260 that circumscribes the inner frame, andincludes a plurality of ventricular anchoring supports 250 that each mayinclude a ventricular anchoring leg 254. In some embodiments, outerframe 260 includes a ring 266 to which ventricular anchoring supports250 are coupled. Ring 266 is defined by a pattern of alternating peaksand troughs, the peaks being fixed to frame 230 at respective couplingpoints 252, e.g., as described hereinabove for frame assembly 22,mutatis mutandis.

Whereas atrial anchoring arms 46 of frame assembly 22 are shown asextending from upstream end 34 of inner frame tubular portion 32, atrialanchoring arms 146 and 246 of frame assemblies 122 and 222,respectively, may extend from sites further downstream. (This differencemay also be made to frame assembly 22, mutatis mutandis.) For example,and as stated above in reference to FIG. 7B, atrial anchoring arms 146may be configured to extend from an intermediate portion of inner frametubular portion 132 and thus also from an intermediate portion ofannular valve body 125. In some embodiments, and as illustrated in FIGS.7A and 7B, atrial anchoring arms 146 may connect to the inner frametubular portion 132 at a single connection location 141, with each arm146 connecting to the tubular portion 132 at a different connectionlocation 141. Atrial anchoring arms 146 may thus extend radially outwardfrom connection locations 141. Similarly, and as also illustrated inFIGS. 7A and 7B, ventricular anchoring legs 154 may connect to the outerframe tubular portion 165 at a single connection location 157, with eachleg 154 connecting to the tubular portion 165 at a different connectionlocation 157. Ventricular anchoring legs 154 may thus extend radiallyoutward from connection locations 157. Inner frame tubular portions 32,132 and 232 are each defined by a repeating pattern of cells thatextends around the central longitudinal axis. In some embodiments, andas shown, inner frame tubular portions 32, 132 and 232 are each definedby two stacked, tessellating rows of cells. In the expanded state ofeach inner frame tubular portion, these cells may be narrower at theirupstream and downstream extremities than midway between theseextremities. For example, and as shown, the cells may be roughly diamondor asteroid in shape. In frame assembly 22, each atrial anchoring arm 46is attached to and extends from a site 35 that is at the upstreamextremity of cells of the upstream row. In contrast, in frame assemblies122 and 222, each atrial anchoring arm 146 or 246 is attached to andextends from a site 135 (assembly 122) or 235 (assembly 222) that is atthe connection between two adjacent cells of the upstream row(alternatively described as being at the upstream extremity of cells ofthe downstream row).

It is hypothesized by the inventors that this lower position of theatrial anchoring arms, while maintaining the length of the lumen of theinner frame tubular portion, advantageously reduces the distance thatthe inner frame tubular portion (i.e., the downstream end thereof)extends into the ventricle of the subject, and thereby reduces alikelihood of inhibiting blood flow out of the ventricle through theleft ventricular outflow tract. It is further hypothesized that thisposition of the atrial anchoring arms reduces radial compression of theinner frame tubular portion by movement of the heart, due to greaterrigidity of the inner frame tubular portion at sites 135 and 235 (whichis supported by two adjacent cells) than at site 35 (which is supportedby only one cell).

As shown, in the expanded state of frame assemblies 22, 122 and 222, theventricular anchoring supports 50, 150, 250 (and thus ventricularanchoring legs 54, 154, 254) are circumferentially staggered (i.e.,angularly offset) with the atrial anchoring arms of the upstream supportportion (46, 146 and 246, respectively). As illustrated in FIG. 7B,locations of connection 141 may thus also be circumferentially staggered(i.e. angularly offset) from locations of connection 157. Thecircumferential staggering of ventricular anchoring supports 50, 150,250 and atrial anchoring arms 46, 146, 246 may allow the ventricularanchoring supports 50 to move in an upstream direction between theatrial anchoring arms during expansion of the inner frame tubularportion (32, 132 and 232, respectively), facilitating application ofgreater sandwiching force on tissue of the native valve. The lowerposition of the atrial anchoring arms of assemblies 122 and 222 includescircumferentially shifting the position of the atrial anchoring arms bythe width of half a cell. In order to maintain the circumferentialstaggering of the atrial anchoring arms 46, 146, 246 and ventricularanchoring legs 54, 154, 254, rings 166 and 266 (and thereby ventricularanchoring supports 150 and 250) are circumferentially shiftedcorrespondingly. As illustrated in FIGS. 7B and 8B, ventricularanchoring supports 150, 250 may extend between rings 166, 266. Moreover,ventricular anchoring supports 150 depicted in FIG. 7B may intersectwith a ring 166 and with ventricular anchoring legs 154 at connectionlocations 157, and may thus act as a strut of outer frame 160. As aresult, whereas the peaks of ring 66 generally align with connectionsbetween adjacent cells of the downstream row of cells of inner frametubular portion 32 (and are fixed to these sites), the peaks of rings166 and 266 are generally aligned midway between these sites (i.e., atspaces of the cellular structure of the inner frame tubular portion). Anappendages 168 (for assembly 122) or 268 (for assembly 222) facilitatefixing of the peak with respect to the tubular structure. In accordancewith embodiments depicted in FIG. 7B, atrial anchoring arms 146 mayinclude no physical connections to other arms 146 or to ventricularanchoring legs 154 beyond the locations 141 at which the atrialanchoring arms 146 connect to the inner frame tubular portion 132.Similarly, and as also depicted in FIG. 7B, ventricular anchoring legs154 may include no physical connections to other legs 154 or to atrialanchoring arms 146 beyond the locations 157 at which the ventricularanchoring legs 154 connect to the outer frame tubular portion 165.

For assembly 122, appendages 168 are defined by inner frame 130 (e.g.,by inner frame tubular portion 132 thereof) and extend (in a downstreamdirection) to the peaks of ring 166, to which they are fixed. Forexample, each appendage 168 may define a valve-frame coupling element131 that is fixed to a respective outer-frame coupling element 161defined by outer frame 260. In some embodiments, appendages 168 extendfrom sites 135. In some embodiments, appendages 168 are integral withinner frame tubular portion 132 and/or in-plane with the inner frametubular portion (e.g., are part of its tubular shape).

For assembly 222, appendages 268 are defined by outer frame 260, andextend (e.g., in an upstream direction) from the peaks of ring 266. Insome embodiments, appendages 268 extend to sites 235, to which they arefixed. For example, each appendage 268 may define an outer-framecoupling element 261 that is fixed to a respective valve-frame couplingelement 231 defined by inner frame 230 (e.g., by inner frame tubularportion 232 thereof). In some embodiments, appendages 268 are integralwith outer frame 260 and/or in-plane with adjacent portions of outerframe 260, such as ring 266.

Therefore, frame assembly 122 defines a hub at site 135, and frameassembly 222 defines a hub at site 235. In some embodiments, apparatustherefore includes a plurality of prosthetic valve leaflets; and a frameassembly, including an inner frame tubular portion (132 or 232) definedby a repeating pattern of cells, the inner frame tubular portionextending circumferentially around longitudinal axis ax1 so as to definea longitudinal lumen, the prosthetic valve leaflets coupled to the innerframe and disposed within the lumen; an outer frame (160 or 260),including a plurality of ventricular anchoring supports (150 or 250),distributed circumferentially around the inner frame tubular portion,each support having a ventricular anchoring leg (154 or 254); anupstream support portion (140 or 240) that includes a plurality ofatrial anchoring arms (146 or 246) that extend radially outward from theinner frame tubular portion; and a plurality of appendages (168 or 268),each having a first end that defines a coupling element (161 or 261) viawhich the inner frame tubular portion is coupled to the outer frame, anda second end; wherein the frame assembly defines a plurality of hubs(135 or 235), distributed circumferentially around the longitudinal axison a plane that is transverse to longitudinal axis ax1, each hub definedby convergence and connection of, (i) two adjacent cells of the innerframe tubular portion, (ii) an arm of the plurality of atrial anchoringarms, and (iii) an appendage of the plurality of appendages.

Reference is made to FIGS. 9A-C, which are schematic illustrations of anprosthetic valve 320 including a frame assembly 322, in accordance withsome embodiments of the invention. Except where noted otherwise, frameassembly 322 is identical to frame assembly 122, and prosthetic valve300 is identical to the prosthetic valve to which frame assembly 122belongs, mutatis mutandis. FIG. 9A is a side-view of prosthetic valve320, and FIG. 9B is an isometric bottom-view of the prosthetic valve.

Frame assembly 122 includes an inner frame 330 that includes an innerframe tubular portion 332 and an upstream support portion 340 that mayinclude a plurality of arms 346, and (ii) an outer frame (e.g., a legframe) 360 that circumscribes the inner frame, and includes a pluralityof ventricular anchoring supports 350 that each may include aventricular anchoring leg 354. In some embodiments, outer frame 360includes a ring 366 to which ventricular anchoring supports 350 arecoupled. Ring 366 is defined by a pattern of alternating peaks andtroughs, the peaks being fixed to frame 330 at respective couplingpoints 352, e.g., as described hereinabove for frame assembly 22 and/orframe assembly 122, mutatis mutandis.

Frame assembly 322 includes an annular upstream support portion 340 thathas an inner portion 342 that extends radially outward from the upstreamportion (e.g., the upstream end) of inner frame tubular portion 332.Upstream support portion 340 further includes one or more fabric pockets344 disposed circumferentially around inner portion 342, each pocket ofthe one or more pockets having an opening that faces a downstreamdirection (i.e., generally toward the downstream end of prosthetic valve320). In the figures, upstream support portion 340 has a single toroidalpocket 344 that extends circumferentially around inner portion 342.

In some embodiments, a covering 323 (e.g., similar to covering 23,described hereinabove, mutatis mutandis) is disposed over arms 346,thereby forming pocket 344. Additionally or alternatively, arms 346 areshaped to form pocket 344 from covering 323. For example, and as shown,arms 346 may curve to form a hook-shape.

In some embodiments, portion 340 has a plurality of separate pockets344, e.g., separated at arms 346. In such embodiments, covering 323 isloosely-fitted (e.g., baggy) between radially-outward parts of arms 346,e.g., compared to inner portion 342, in which the covering is moreclosely-fitted between radially-inward parts of the arms.

FIG. 9C shows prosthetic valve 320 implanted at native valve 10. Pocket344 is shaped and arranged to billow in response to perivalvular flow302 of blood in an upstream direction. If ventricular systole forcesblood in ventricle 8 between prosthetic valve 320 and native valve 10,that blood inflates pocket 344 and presses it (e.g., covering 323 and/orthe radially-outward part of arm 346) against tissue of atrium 6 (e.g.,against the atrial wall), thereby increasing sealing responsively. It ishypothesized by the inventors that the shape and orientation of pocket344 (e.g., the hook-shape of arms 346) facilitates this pressingradially-outward in response to the pocket's receipt of upstream-flowingblood.

Pocket(s) 344 may be used in combination with any of the prostheticvalves described herein, mutatis mutandis.

Reference is again made to FIGS. 1A-9C. It is to be noted that unlessspecifically stated otherwise, the term “radially outward” (e.g., usedto describe upstream support portion 40 and ventricular anchoring legs54) means portions of the element are disposed progressively furtheroutward from a central point (such as longitudinal axis ax1 or innerframe tubular portion 32), but does not necessarily mean disposed at 90degrees with respect to longitudinal axis ax1. For example, ventricularanchoring legs 54 may extend radially outward at 90 degrees with respectto longitudinal axis ax1, but may alternatively extend radially outwardat a shallower angle with respect to the longitudinal axis.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1-72. (canceled)
 73. A prosthetic valve for implantation within a nativeheart valve, the prosthetic valve being configured for expansion from aradially-contracted state to a radially-expanded state, wherein theprosthetic valve comprises: an annular valve body having an upstreamend, a downstream end opposite from the upstream end, and anintermediate portion extending between the upstream end and thedownstream end; a plurality of atrial anchoring arms configured toextend radially outward from the annular valve body, each atrialanchoring arm having a proximal arm end secured to the annular valvebody and a terminal arm end opposite from the proximal arm end, whereinat least one atrial anchoring arm extends from a single location ofconnection to the annular valve body and comprises: a first arm segmentconfigured to extend in a first upstream direction, the first armsegment including the proximal arm end of the at least one atrialanchoring arm, a second arm segment configured to extend in a downstreamdirection, and a third arm segment configured to extend in a secondupstream direction, the third arm segment including the terminal arm endof the at least one atrial anchoring arm, wherein the terminal arm endof the at least one atrial anchoring arm is configured to be situatedupstream from the rest of the at least one atrial anchoring arm when theprosthetic valve is in the radially-expanded state; and a plurality ofventricular anchoring legs configured to extend radially outward fromthe annular valve body, each ventricular anchoring leg having a proximalleg end secured to the annular valve body and a terminal leg endopposite from the proximal leg end, wherein a proximal portion of atleast one ventricular anchoring leg is configured to extend in a thirdupstream direction, the proximal portion including the proximal leg endof the at least one ventricular anchoring leg, wherein the at least oneatrial anchoring arm is configured for outward radial deflectionindependent of the other atrial anchoring arms and the at least oneventricular anchoring leg is configured for outward radial deflectionindependent of the other ventricular anchoring legs.
 74. The prostheticvalve of claim 73, wherein each atrial anchoring arm extends from asingle location of connection to the intermediate portion of the annularvalve body, and wherein each ventricular anchoring leg extends from asingle location of connection to the intermediate portion of the annularvalve body.
 75. The prosthetic valve of claim 74, wherein the locationsof connection from which the atrial anchoring arms extend from theintermediate portion of the annular valve body are offset at a regularinterval, relative to a circumferential direction of the prostheticvalve, from the locations of connection from which the ventricularanchoring legs extend from the intermediate portion of the annular valvebody.
 76. The prosthetic valve of claim 73, wherein the at least oneatrial anchoring arm is configured to extend radially outward beyond theterminal leg ends of the ventricular anchoring legs such that theterminal arm end of the at least one atrial anchoring arm forms theouter-most portion of the prosthetic valve, relative to a longitudinalaxis extending through the center of the annular valve body.
 77. Theprosthetic valve of claim 73, wherein the second arm segment iscontiguous with the first arm segment and the third arm segment.
 78. Theprosthetic valve of claim 73, wherein a leg length extending between theproximal leg end and terminal leg end of the at least one ventricularanchoring leg is configured to extend upstream from the annular valvebody when the prosthetic valve is in the radially-expanded state. 79.The prosthetic valve of claim 73, wherein the prosthetic valve isconfigured to be symmetrical about a longitudinal axis extending throughthe center of the annular valve body.
 80. A prosthetic valve forimplantation within a native heart valve, the prosthetic valvecomprising: an annular outer frame having an upstream end, a downstreamend opposite from the upstream end of the annular outer frame, and anintermediate portion extending between the upstream end and downstreamend of the annular outer frame; an inner frame situated at leastpartially within the annular outer frame, the inner frame having anupstream end, a downstream end opposite from the upstream end of theinner frame, and an intermediate portion extending between the upstreamend and downstream end of the inner frame, wherein the downstream end ofthe annular outer frame is free from connections to the inner frame; aplurality of ventricular anchoring legs configured to extend from theintermediate portion of the annular outer frame, wherein at least oneventricular anchoring leg is configured for outward radial deflectionindependent of the other ventricular anchoring legs; and a plurality ofatrial anchoring arms configured to extend from the intermediate portionof the inner frame, wherein at least one atrial anchoring arm isconfigured for outward radial deflection independent of the other atrialanchoring arms, wherein the prosthetic valve comprises at least as manyventricular anchoring legs as atrial anchoring arms.
 81. The prostheticvalve of claim 80, wherein each ventricular anchoring leg extends from asingle location of connection to the intermediate portion of the annularouter frame, and wherein each atrial anchoring arm extends from a singlelocation of connection to the intermediate portion of the inner frame.82. The prosthetic valve of claim 80, wherein the at least one atrialanchoring arm is configured to extend radially outward beyond terminalleg ends of the ventricular anchoring legs such that a terminal arm endof the at least one atrial anchoring arm forms the outer-most portion ofthe prosthetic valve, relative to a longitudinal axis extending throughthe center of the annular outer frame.
 83. The prosthetic valve of claim82, wherein the terminal arm end of the at least one atrial anchoringarm is configured to be situated upstream from the rest of the at leastone atrial anchoring arm when the prosthetic valve is in aradially-expanded state.
 84. The prosthetic valve of claim 80, whereinan axial length between the upstream and downstream ends of the innerframe is greater than an axial length between the upstream anddownstream ends of the annular outer frame, and wherein the inner frameis configured to extend in an upstream direction beyond the upstream endof the annular outer frame.
 85. The prosthetic valve of claim 80,wherein each of the inner frame and annular outer frame includes aplurality of struts intersecting at junctions to form closed cells, theinner frame having closed cells of a first shape and the outer framehaving closed cells of a second shape different than the first shape.86. The prosthetic valve of claim 80, wherein the prosthetic valve isconfigured to be symmetrical about a longitudinal axis extending throughthe center of the annular outer frame.
 87. A prosthetic valve forimplantation within a native heart valve, the prosthetic valvecomprising: an annular valve body having an upstream end, a downstreamend opposite from the upstream end, and an intermediate portionextending between the upstream end and the downstream end; a pluralityof atrial anchoring arms configured to extend radially outward from theintermediate portion of the annular valve body, wherein at least oneatrial anchoring arm is configured for outward radial deflectionindependent of the other atrial anchoring arms; and a plurality ofventricular anchoring legs configured to extend radially outward fromthe intermediate portion of the annular valve body, wherein at least oneventricular anchoring leg is configured for outward radial deflectionindependent of the other ventricular anchoring legs, wherein theprosthetic valve comprises at least as many ventricular anchoring legsas atrial anchoring arms, and wherein a portion of the at least oneatrial anchoring arm is configured to be situated at the same axialposition along a longitudinal axis of the annular valve body as aportion of the at least one ventricular anchoring leg.
 88. Theprosthetic valve of claim 87, wherein each atrial anchoring arm extendsfrom a single location of connection to the intermediate portion of theannular valve body, and wherein each ventricular anchoring leg extendsfrom a single location of connection to the intermediate portion of theannular valve body.
 89. The prosthetic valve of claim 87, wherein the atleast one atrial anchoring arm is configured to extend radially outwardbeyond terminal leg ends of the ventricular anchoring legs such that aterminal arm end of the at least one atrial anchoring arm forms theouter-most portion of the prosthetic valve, relative to a longitudinalaxis extending through the center of the annular valve body.
 90. Theprosthetic valve of claim 89, wherein the terminal arm end of the atleast one atrial anchoring arm is configured to be situated upstreamfrom the rest of the at least one atrial anchoring arm when theprosthetic valve is in a radially-expanded state.
 91. The prostheticvalve of claim 87, wherein the prosthetic valve is configured to besymmetrical about a longitudinal axis extending through the center ofthe annular valve body.
 92. The prosthetic valve of claim 87, wherein aleg length extending between a proximal leg end and a terminal leg endof the at least one ventricular anchoring leg is configured to extendupstream from the annular valve body when the prosthetic valve is in aradially-expanded state.